Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development
Abstract
1. Introduction
2. Events Triggering Hepatocyte Death, Release of DAMPs and Inflammatory Signals
3. Activation of KCs and Inflammatory Signaling
3.1. Inflammatory Signals from Kupffer Cells and Other Inflammation-Related Cells
3.2. Proinflammatory Cytokines
3.3. Anti-Inflammatory Cytokines
4. Sterile Inflammation and Inflammasome Complex
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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DAMPs | Receptor | Function |
---|---|---|
ATP, UTP | P2RX7, P2Y2, NLRP3 | Purine metabolites |
NLRP3 inflammasome activation Neutrophils infiltration | ||
Defensins | TLR4, CCR6 | |
Fatty acids | TLR4 | Inflammatory signaling |
HSPs (HSPA1A, HSPB1) | TLR2, TLR4, CD14, CD91 | Intracellular chaperons Adjuvants |
CRT, ERp57 | CD91 | ER chaperons |
HMGB1 | TLR4, RAGE, CD24/SIGLEC10 | Multifunctional nuclear factor Profibrogenic effects Anti-inflammatory function (binding to RAGE, CD24/SIGLEC10) |
IL-33 | IL1RL1 | Anti-inflammatory function |
mtDNA | NLRP3, TLR9 | NLRP3 inflammasome activation |
nDNA | NLRP3, TLR9 | NLRP3 inflammasome activation HSCs activation |
N-formyl peptides | FPR1, TLR9 | Mitochondrial polypeptides |
S1P | S1PR | Anti-apoptotic stimulus |
Uric acid | NLRP3 | Purine catabolite Pro-inflammatory metabolite |
Peroxiredoxin-1 | TLR2, TLR4, NLRP3 | NF-κB and NLRP3 inflammasome signaling |
Histones | TLR2, TLR4 | NLRP3 inflammasome activation |
Inflammatory Signal | Producing Cells | Target Cells | Role |
---|---|---|---|
TNF-α | KCs, M1 macrophages, MAIT cells | Activated HSCs | Pro-survival of aHSCs |
TGF-β1 | aHSCs, KCs, hepatocytes, LSECs | HSCs, KCs | HSCs activation, upregulation of matrix-producing genes |
IL-17 | Th cells, MAIT cells | KCs, M1 macrophages | Indirectly HSCs activation, HSCs collagen type I deposition |
IL-10 | M2 macrophages | M2 macrophages, aHSCs | Downregulating pro-inflammatory processes, senescence of aHSCs |
IL-6 | KCs, M1 macrophages, myofibroblasts | Hepatocytes | Inhibition of apoptosis and regeneration stimulation of hepatocytes |
IL-1β | KCs | HSCs, hepatocytes | Pro-inflammatory effect, acts together with Il-1α, HSCs proliferation |
IL-1α | KCs | HSCs, hepatocytes | Pro-inflammatory effect, acts together with Il-1α |
IL-22 | KCs, innate immunity cells | Hepatocytes | Pro-survival signals on hepatocytes |
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Ignat, S.-R.; Dinescu, S.; Hermenean, A.; Costache, M. Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development. Cells 2020, 9, 461. https://doi.org/10.3390/cells9020461
Ignat S-R, Dinescu S, Hermenean A, Costache M. Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development. Cells. 2020; 9(2):461. https://doi.org/10.3390/cells9020461
Chicago/Turabian StyleIgnat, Simona-Rebeca, Sorina Dinescu, Anca Hermenean, and Marieta Costache. 2020. "Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development" Cells 9, no. 2: 461. https://doi.org/10.3390/cells9020461
APA StyleIgnat, S.-R., Dinescu, S., Hermenean, A., & Costache, M. (2020). Cellular Interplay as a Consequence of Inflammatory Signals Leading to Liver Fibrosis Development. Cells, 9(2), 461. https://doi.org/10.3390/cells9020461