Search Results (752)

Proteomic profiling using ultrafast chromatography–mass spectrometry provides valuable insights into plant responses to abiotic factors by linking molecular changes with physiological outcomes. Nanopriming, a novel approach involving the treatment of seeds with nanoparticles, has demonstrated potential for enhancing plant metabolism and productivity. However, the molecular mechanisms underlying nanoparticle-induced effects remain poorly understood. In this study, we investigated the impact of gold nanoparticle (Au-NP) seed priming on the proteome of wheat (Triticum aestivum L.) seedlings. Differentially regulated proteins (DRPs) were identified, revealing a pronounced reorganization of the photosynthetic apparatus (PSA). Both the light-dependent reactions and the Calvin cycle were affected, with significant upregulation of chloroplast-associated protein complexes, including PsbC (CP43), chlorophyll a/b-binding proteins, Photosystem I subunits (PsaA and PsaB), and the γ-subunit of ATP synthase. The large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) exhibited over a threefold increase in expression in Au-NP-treated seedlings. The proteomic changes in the large subunit RuBisCo L were corroborated by transcriptomic data. Importantly, the proteomic changes were supported by physiological and biochemical analyses, ultrastructural modifications in chloroplasts, and increased photosynthetic activity. Our findings suggest that Au-NP nanopriming triggers coordinated molecular responses, enhancing the functional activity of the PSA. Identified DRPs may serve as potential biomarkers for further elucidation of nanopriming mechanisms and for the development of precision strategies to improve crop productivity. Full article

Human leukocyte antigen class I (HLA-I) molecules present intracellular peptides on the cell surface to enable CD8+ T cells to effectively control viral infections. Many viruses disrupt this antigen presentation pathway to evade immune detection. In this study, we demonstrate that SARS-CoV-2 Nsp1 impairs both the constitutive and interferon-γ (IFN-γ)-induced upregulation of HLA-I. Moreover, Nsp1 also blocks IFN-γ-induced expression of HLA-II. We found that, contrary to previously published work, the early SARS-CoV-2 B 1.1.7 Alpha variant lacking the accessory protein ORF8 retained full capacity to downregulate HLA-I, comparable to an ORF8-expressing wild-type isolate. While ectopic overexpression of ORF8 could reduce HLA-I surface levels, this effect was only observed at high expression levels. In contrast, moderate expression of the viral protein Nsp1 was sufficient to potently suppress both basal and IFN-γ-induced HLA-I, as well as HLA-II expression. To probe the underlying mechanism, we analyzed HLA-I-associated genes in previously published RNA-sequencing datasets and confirmed that Nsp1 reduces expression of components required for HLA-I biosynthesis and antigen processing. These findings identify Nsp1 as a key factor that impairs antigen presentation pathways, potentially contributing to the ability of SARS-CoV-2 to modulate immune recognition. Full article

Background/Objectives: Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids—SSF) remain unclear. This study characterized SSF’s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC/Q-Orbitrap/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4⁺/CD8⁺ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-α, IFN-γ, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR/MyD88/NF-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy. Full article

Background: Fowl typhoid (FT), a septicemic infection caused by Salmonella Gallinarum (SG), and H9N2 avian influenza are two economically important diseases that significantly affect the global poultry industry. Methods: We exploited the live attenuated Salmonella Gallinarum (SG) mutant JOL3062 (SG: ∆lon ∆pagL ∆asd) as a delivery system for H9N2 antigens to induce an immunoprotective response against both H9N2 and FT. To enhance immune protection against H9N2, a prokaryotic and eukaryotic dual expression plasmid, pJHL270, was employed. The hemagglutinin (HA) consensus sequence from South Korean avian influenza A virus (AIV) was cloned under the Ptrc promoter for prokaryotic expression, and the B cell epitope of neuraminidase (NA) linked with matrix protein 2 (M2e) was placed for eukaryotic expression. In vitro and in vivo expressions of the H9N2 antigens were validated by qRT-PCR and Western blot, respectively. Results: Oral immunization with JOL3121 induced a significant increase in SG and H9N2-specific serum IgY and cloacal swab IgA antibodies, confirming humoral and mucosal immune responses. Furthermore, FACS analysis showed increased CD4+ and CD8+ T cell populations. On day 28 post-immunization, there was a substantial rise in the hemagglutination inhibition titer in the immunized birds, demonstrating neutralization capabilities of immunization. Both IFN-γ and IL-4 demonstrated a significant increase, indicating a balance of Th1 and Th2 responses. Intranasal challenge with the H9N2 Y280 strain resulted in minimal to no clinical signs with significantly lower lung viral titer in the JOL3121 group. Upon SG wildtype challenge, the immunized birds in the JOL3121 group yielded 20% mortality, while 80% mortality was recorded in the PBS control group. Additionally, bacterial load in the spleen and liver was significantly lower in the immunized birds. Conclusions: The current vaccine model, designed with a host-specific pathogen, SG, delivers a robust immune boost that could enhance dual protection against FT and H9N2 infection, both being significant diseases in poultry, as well as ensure public health. Full article

Background: Toxoplasma gondii (T. gondii) causes severe disease in immunocompromised individuals and pregnant women, underscoring the urgent need for effective vaccines against toxoplasmosis. The dense granule protein 5 (GRA5) of T. gondii plays a key role in parasitic cyst formation. Methods: This study evaluated the protective immune responses induced by a virus-like particle (VLP) vaccine expressing the T. gondii-derived antigen GRA5 in a mouse model challenged with the ME49 strain of T. gondii. GRA5 VLPs were generated using a baculovirus expression system, and VLP formation was confirmed by Western blotting and visualized using transmission electron microscopy. Mice were intranasally immunized with GRA5 VLPs three times at 4-week intervals to induce immune responses, followed by infection with T. gondii ME49. Results: Intranasal immunization with GRA5 VLPs induced parasite-specific IgG antibody responses in the serum and both IgG and IgA antibody responses in the brain. Compared to the non-immunized group, immunized mice exhibited significantly higher levels of germinal center B cells and antibody-secreting cell responses. Moreover, the VLP vaccine suppressed the production of IFN-γ and IL-6 cytokines, leading to a significant reduction in brain inflammation and decreased cyst counts following lethal challenge with T. gondii ME49 infection. Conclusion: These findings suggest that the GRA5 VLP vaccine derived from T. gondii elicits a protective immune response, highlighting its potential as an effective vaccine candidate against toxoplasmosis. Full article

Estrogen-related receptor γ (ERRγ) has been reported to regulate various inflammation-related diseases. Herein, we attempted to evaluate the effects of DN200434 as a modulator for ERRγ in mice with atopic dermatitis (AD). Levels of mRNA and protein expression for ERRγ were evaluated in normal and DNCB-induced AD-diagnosed skin. The effects of DN200434 on the chemokines, inflammatory cytokines, and AKT/MAPK/NFκB pathway signaling were investigated in TNF-α/IFN-γ-treated HaCaT cells. DNCB-induced AD mice received DN200434 intraperitoneally for 10 days. Epidermal thickness at the dorsal aspect of the inflamed skin, spleen index, serum IgE levels, and proinflammatory cytokine levels in the skin lesions were measured. Histopathological evaluations, including assessments of epidermal hyperplasia, dermal inflammation, hyperkeratosis, folliculitis, and mast cell counts, were performed to confirm diagnostic features. Significant elevations in ERRγ expression at the RNA and protein levels were observed in DNCB-induced AD lesions. DN200434 suppressed chemokine and inflammatory cytokine expression and inhibited the elevated phosphorylation levels of AKT, ERK, p38, and NFκB in TNF-α/IFN-γ-treated HaCaT cells. Treatment with DN200434 alleviated DNCB-induced AD symptoms. The histopathological score and levels of infiltrated mast cells were also markedly lower in DN200434-treated AD mice than in vehicle-treated AD mice. Consistently, DN200434 reduced the serum IgE level and mRNA expression of TNFα and IL-6 in AD-diagnosed lesions. Collectively, our findings indicated the feasibility of ERRγ as a therapeutic target for the regulation of AD and that DN200434 can be a useful therapeutic agent in treating AD. Full article

The deamidation rate is relatively high for Asn residues with Phe as the C-terminal adjacent residue in γS-crystallin, which is one of the human crystalline lens proteins. However, peptide-based experiments indicated that bulky amino acid residues on the C-terminal side impaired Asn deamination. In this study, we hypothesized that the side chain of Phe affects the Asn deamidation rate and investigated the succinimide formation process using quantum chemical calculations. The B3LYP density functional theory was used to obtain optimized geometries of energy minima and transition states, and MP2 and M06-2X calculations were used to obtain the single-point energy. Activation barriers and rate-determining step changed depending on the orientation of the Phe side chain. In pathways where an interaction occurred between the benzene ring and the amide group of the Asn residue, the activation barrier was lower than in pathways where this interaction did not occur. Since the aromatic ring is oriented toward the Asn side in experimentally determined structures of γS-crystallin, the above interaction is considered to enhance the Asn deamidation. Full article

Atherosclerosis (AS), a progressive inflammatory disease of coronary arteries, the aorta, and the internal carotid artery, is considered one of the main contributors to cardiovascular disorders. Blood flow is restricted by accumulating lipid-rich macrophages (foam cells), calcium, fibrin, and cellular debris into plaques on the intima of arterial walls. Butyrate maintains gut barrier integrity and modulates immune responses. Butyrate regulates G-protein-coupled receptor (GPCR) signaling and activates nuclear factor kappa-B (NF-κB), activator protein-1 (AP-1), and interferon regulatory factors (IFRs) involved in the production of proinflammatory cytokines. Depending on the inflammatory stimuli, butyrate may also inactivate NF-κB, resulting in the suppression of proinflammatory cytokines and the stimulation of anti-inflammatory cytokines. Butyrate modulates mitogen-activated protein kinase (MAPK) to promote or suppress macrophage inflammation, muscle cell growth, apoptosis, and the uptake of oxidized low-density lipoprotein (ox-LDL) in macrophages. Activation of the peroxisome proliferator-activated receptor γ (PPARγ) pathway plays a role in lipid metabolism, inflammation, and cell differentiation. Butyrate inhibits interferon γ (IFN-γ) signaling and suppresses NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) involved in inflammation and scar tissue formation. The dual role of butyrate in AS is discussed by addressing the interactions between butyrate, intestinal epithelial cells (IECs), endothelial cells (ECs) of the main arteries, and immune cells. Signals generated from these interactions may be applied in the diagnosis and intervention of AS. Reporters to detect early AS is suggested. This narrative review covers the most recent findings published in PubMed and Crossref databases. Full article

Bovine alphaherpesvirus 1 (BoAHV-1) is a promising oncolytic virus that can infect the human lung carcinoma cell line A549. In an effort to adapt the virus to grow more rapidly in these cells through the serial passaging of viral progeny, we were unsuccessful. Here, we found that extracellular vesicles (EVs) secreted by BoAHV-1-infected A549 cells (referred to as EDVs) contain 59 viral proteins, including both viral structure proteins (such as gC and gD) and viral regulatory proteins (such as bICP4 and bICP22), as identified via a proteomic analysis. These EDVs can bind to and enter target cells, inhibit viral particles binding to cells, and stimulate the production of IFN-α and IFN-β in A549 cells. When EDVs are inoculated into rabbits via either the conjunctival sacs or intravenously, they can be readily detected in neurons within the trigeminal ganglia (TG), where they reduce viral replication and promote the transcription of IFN-γ. Furthermore, incorporation of the known anti-herpesvirus drug Acyclovir (ACY) into the EDVs leads to synergistically enhanced antiviral efficacy. Collectively, the EDVs exhibit antiviral effects by blocking viral binding to target cells and stimulating the innate immune response, thereby leading to the failure of the serial passaging of viral progeny in these cells, and these EDVs may serve as a promising vector for delivering drugs targeting TG tissues for antiviral purposes. Full article

Background: Cancer stem cells (CSCs) are a subpopulation of cancer cells known for their self-renewal capacity, tumorigenicity, and resistance to treatment. Toll-like receptor 3 (TLR3) plays a complex role in cancer, exhibiting both pro-apoptotic and pro-tumorigenic effects. This study investigates the pro-tumorigenic role of TLR3, specifically its impact on CSCs in head and neck cancer. Methods: We have investigated Detroit 562, FaDu and SQ20B cell lines, the latter being stably transfected with a plasmid containing inducible shRNA for TLR3, by cultivating them to form tumor spheres in order to study CSCs. Results: Our findings demonstrate that TLR3 activation promotes stemness in head and neck cancer cell lines. This is evidenced by increased tumor sphere formation, promotion of epithelial-to-mesenchymal transition (EMT), upregulated stemness gene expression, and elevated aldehyde dehydrogenase (ALDH) activity. Conditional TLR3 knockdown abolished tumor sphere formation, confirming its important role. Furthermore, TLR3 activation triggers the secretion of damage-associated molecular patterns (DAMPs) into the tumor microenvironment, leading to increased cancer cell migration. This was inhibited by DAMP inhibitors. In patient tissue samples, we observed co-localization of TLR3 with stemness markers CD133 and ALDH1, as well as with heat shock protein 70 (HSP70) and receptor for advanced glycation end products (RAGE). We then explored potential CSC-targeted therapies, initially combining the apoptosis inducer poly (I:C) with DAMP inhibitors and γ-irradiation. While this combination proved effective in adherent cells, it failed to eliminate tumor spheres. Nevertheless, we discovered that proton radiotherapy, particularly when combined with aspirin (HMGB1 inhibitor) and poly (I:C), effectively eliminates CSCs. Conclusions: This novel combination holds promise for the development of new therapeutic strategies for head and neck cancers, particularly given the promising results of proton therapy in treating this disease. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited therapeutic options. Current therapies (pirfenidone, nintedanib) exhibit modest efficacy and significant side effects, underscoring the need for novel strategies targeting early pathogenic drivers. Saroglitazar (SGZ), a dual PPARα/γ agonist with anti-inflammatory properties approved for diabetic dyslipidemia, has not been explored for IPF. We aimed to investigate SGZ’s therapeutic potential in pulmonary fibrosis and elucidate its mechanisms of action. Materials and Methods: Using a bleomycin (BLM)-induced murine pulmonary fibrosis model, we administered SGZ therapeutically. A histopathological assessment (H&E, Masson’s trichrome, collagen I immunofluorescence), Western blotting, and qRT-PCR analyzed the fibrosis progression and inflammatory markers. Flow cytometry evaluated the macrophage polarization. In vitro studies used RAW264.7 macrophages stimulated with BLM/LPS and MRC-5 fibroblast co-cultures. The NF-κB/NLRP3 pathway activation was assessed through protein and gene expression. Results: SGZ significantly attenuated BLM-induced histopathological hallmarks, including alveolar wall thickening, collagen deposition, and inflammatory infiltration. Fibrotic markers (OPN, α-SMA) and pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) were downregulated in the SGZ-treated mice. Mechanistically, SGZ suppressed the M1 macrophage polarization (reduced CD86⁺ populations) and inhibited the NF-κB/NLRP3 pathway activation in the alveolar macrophages. In the RAW264.7 cells, SGZ decreased the NLRP3 inflammasome components (ASC, cleaved IL-1β) and cytokine secretion. Co-cultures demonstrated that the SGZ-treated macrophage supernatants suppressed the fibroblast activation (α-SMA, collagen I) in MRC-5 cells. Conclusions: SGZ attenuates pulmonary fibrosis by suppressing macrophage-driven inflammation via NF-κB/NLRP3 inhibition and disrupting the macrophage–fibroblast crosstalk. These findings nominate SGZ as a promising candidate for preclinical optimization and future clinical evaluation in IPF. Full article

Background/Objectives: Degenerative arthritis is a chronic inflammatory disease marked by tissue degradation and vascular fibrosis. Macrophages play a central role in the inflammatory response by releasing mediators such as nitric oxide (NO), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and prostaglandin E2 (PGE2). This study aimed to investigate the anti-inflammatory potential of BTEX-K, a formulation of dried red ginseng combined with alpha-galactosidase, in lipopolysaccharide (LPS)-stimulated cells. Methods: LPS-treated immune cells were used to assess the anti-inflammatory effects of BTEX-K. The levels of NO, IL-6, TNF-α, and PGE2 were measured following BTEX-K treatment. The protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was evaluated. Cytotoxicity assays were conducted to determine whether the observed effects were due to cell viability loss. The involvement of MAPK signaling and NF-κB pathway modulation was examined by analyzing JNK phosphorylation, IκB degradation, and PPAR-γ expression. Results: BTEX-K significantly reduced the production of NO, IL-6, TNF-α, and PGE2 in LPS-treated cells without inducing cytotoxicity. The protein expression levels of iNOS and COX-2 were also suppressed. Furthermore, BTEX-K inhibited the LPS-induced phosphorylation of JNK in the MAPK pathway. It restored IκB levels and suppressed NF-κB activation by preventing the downregulation of PPAR-γ. Conclusions: BTEX-K demonstrates notable anti-inflammatory effects by inhibiting key inflammatory mediators and signaling pathways in immune cells. These findings support its therapeutic potential in mitigating inflammation-related symptoms, including pain, swelling, and redness, commonly seen in degenerative arthritis. Full article

Background: Intestinal epithelial barrier (IEB) dysfunction is related to multiple gastrointestinal disorders, notably inflammatory bowel disease (IBD). Betulinic acid (BA), a compound derived from birch bark, has demonstrated potential therapeutic benefits in IBD. Nevertheless, the impact of BA on IEB function has not been fully elucidated. Methods: The current study aimed to explore the potential underlying mechanisms of BA in dextran sodium sulfate (DSS)-induced IBD in mice and co-culture models involving Caco-2/HT29-MTX-E12 cell monolayers or mouse intestinal organoids (IOs) in conjunction with macrophages stimulated by lipopolysaccharide (LPS). Results: In vivo, BA treatment significantly improved body weight and colon length, alleviated disease activity index (DAI) scores, and reduced colonic histopathological injury in IBD mice. In vitro, BA reduced the flux of FITC-dextran; increased the TEER; and decreased the production of IL-6, IL-1β, and TNF-α while increasing IL-10 mRNA levels. Additionally, BA enhanced IEB formation by upregulating ZO-1, occludin (OCLN), and claudin-1 (CLDN1). Molecular docking studies revealed significant docking scores and interactions between BA and PPAR-γ. Moreover, BA significantly upregulated PPAR-γ protein expression, decreased NF-κB and MLC2 phosphorylation, and reduced MLCK protein expression. However, this effect was reversed by GW9662, an effective PPAR-γ antagonist. Conclusions: The findings reveal that BA mitigates IBD by safeguarding the intestinal barrier against dysfunction. This effect may be attributed to its ability to suppress inflammation and enhance the expression of tight junction proteins by modulating the PPAR-γ/NF-κB signaling pathway. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder marked by the degeneration of dopaminergic neurons in the substantia nigra, leading to decreased dopamine levels in the striatum and causing a range of motor and non-motor impairments. Although the molecular mechanisms driving PD progression remain incompletely understood, emerging evidence suggests that the buildup of nuclear DNA damage, especially DNA double-strand breaks (DDSBs), plays a key role in contributing neurodegeneration, promoting senescence and neuroinflammation. Despite the pathogenic role for DDSB in neurodegenerative disease, targeting DNA repair mechanisms in PD is largely unexplored as a therapeutic approach. Ataxia telangiectasia mutated (ATM), a key kinase in the DNA damage response (DDR), plays a crucial role in neurodegeneration. In this study, we evaluated the therapeutic potential of AZD1390, a highly selective and brain-penetrant ATM inhibitor, in reducing neuroinflammation and improving behavioral outcomes in a mouse model of α-synucleinopathy. Four-month-old C57BL/6J mice were unilaterally injected with either an empty AAV1/2 vector (control) or AAV1/2 expressing human A53T α-synuclein to the substantia nigra, followed by daily AZD1390 treatment for six weeks. In AZD1390-treated α-synuclein mice, we observed a significant reduction in the protein level of γ-H2AX, a DDSB marker, along with downregulation of senescence-associated markers, such as p53, Cdkn1a, and NF-κB, suggesting improved genomic integrity and attenuation of cellular senescence, indicating enhanced genomic stability and reduced cellular aging. AZD1390 also significantly dampened neuroinflammatory responses, evidenced by decreased expression of key pro-inflammatory cytokines and chemokines. Interestingly, mice treated with AZD1390 showed significant improvements in behavioral asymmetry and motor deficits, indicating functional recovery. Overall, these results suggest that targeting the DDR via ATM inhibition reduces genotoxic stress, suppresses neuroinflammation, and improves behavioral outcomes in a mouse model of α-synucleinopathy. These findings underscore the therapeutic potential of DDR modulation in PD and related synucleinopathy. Full article

Sjögren’s disease (SjD) is an autoimmune disease of exocrine tissues. Prior research has shown that ETS proto-oncogene 1 (ETS1), STAT1, and IL33 may contribute to the disease’s pathology. However, the regulatory mechanisms of these genes remain poorly characterized. Our objective was to explore the mechanisms of SjD pathology and to identify dysfunctional regulators of these genes by immunostimulation of SjD and sicca relevant cell lines. We used immortalized salivary gland epithelial cell lines (iSGECs) from Sjögren’s disease (pSS1) and sicca (nSS2) patients, previously developed in our lab, and control cell line A253 to dose with immunostimulants IFN-γ or poly(I:C) (0 to 1000 ng/mL and 0 to 1000 µg/mL, respectively) over a 72 h time course. Gene expression was determined using qRT-PCR delta-delta-CT method based on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for mRNA and U6 small nuclear RNA 1 (U6) for miRNA, using normalized relative fold changes 48 h post-immunostimulation. Protein expression was quantified 72 h post-stimulation by Western blotting. Reference-based RNA-seq of immunostimulated pSS1 and nSS2 cells was performed to characterize the reactome of genes conserved across all used doses. The expression of ETS1 and STAT1 protein was upregulated (p < 0.05) in IFN-γ-treated pSS1 and nSS2, as compared to A253 cells. IFN-γ-treated nSS2 cell showed significant IL33 upregulation. Also, IL33 had a correlated (p < 0.01) U-shaped response for low-mid-range doses for IFN-γ- and poly(I:C)-treated pSS1 cells. RNA-seq showed 175 conserved differentially expressed (DE) genes between nSS2 and pSS1 immunostimulated cells. Of these, 44 were shown to interact and 39 were more abundant (p < 0.05) in pSS1 cells. Western blotting demonstrated nSS2 cells expressing ETS1 uniformly across treatments compared to pSS1 cells, despite similar mRNA abundance. miR-145b and miR-193b were significantly under-expressed in IFN-γ-treated nSS2 cells compared to pSS1 cells (p < 0.01). ETS1 and IL33 showed disproportionate mRNA and protein abundances between immunostimulated Sjögren’s disease-derived (pSS1), and sicca-derived (nSS2) cell lines. Such differences could be explained by higher levels of miR-145b and miR-193b present in pSS1 cells. Also, RNA-seq results suggested an increased sensitivity of pSS1 cells to immunostimulation. These results reflect current pathobiology aspects, confirming the relevance of immortalized salivary gland epithelial cell lines. Full article