Next Article in Journal
Calcium-Sensing Receptor (CaSR), Its Impact on Inflammation and the Consequences on Cardiovascular Health
Next Article in Special Issue
Control of the Autophagy Pathway in Osteoarthritis: Key Regulators, Therapeutic Targets and Therapeutic Strategies
Previous Article in Journal
Structure of the Signal Transduction Domain in Second-Generation CAR Regulates the Input Efficiency of CAR Signals
Previous Article in Special Issue
Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis
Open AccessArticle

Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes

1
Department of Trauma, Hand and Reconstructive Surgery, Experimental Trauma Surgery, Jena University Hospital, Friedrich-Schiller-University Jena, 07747 Jena, Germany
2
Institute of Immunology, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany
3
Institute of Physiology 1/Neurophysiology, Jena University Hospital, Friedrich-Schiller-University Jena, 07743 Jena, Germany
4
Clinic of Trauma, Orthopedic and Septic Surgery, Hospital St. Georg gGmbH, 04129 Leipzig, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Nicola Veronese
Int. J. Mol. Sci. 2021, 22(5), 2477; https://doi.org/10.3390/ijms22052477
Received: 20 January 2021 / Revised: 25 February 2021 / Accepted: 25 February 2021 / Published: 1 March 2021
(This article belongs to the Special Issue Osteoarthritis: From Molecular Pathways to Therapeutic Advances)
Interleukin (IL)-1β is an important pro-inflammatory cytokine in the progression of osteoarthritis (OA), which impairs mitochondrial function and induces the production of nitric oxide (NO) in chondrocytes. The aim was to investigate if blockade of NO production prevents IL-1β-induced mitochondrial dysfunction in chondrocytes and whether cAMP and AMP-activated protein kinase (AMPK) affects NO production and mitochondrial function. Isolated human OA chondrocytes were stimulated with IL-1β in combination with/without forskolin, L-NIL, AMPK activator or inhibitor. The release of NO, IL-6, PGE2, MMP3, and the expression of iNOS were measured by ELISA or Western blot. Parameters of mitochondrial respiration were measured using a seahorse analyzer. IL-1β significantly induced NO release and mitochondrial dysfunction. Inhibition of iNOS by L-NIL prevented IL-1β-induced NO release and mitochondrial dysfunction but not IL-1β-induced release of IL-6, PGE2, and MMP3. Enhancement of cAMP by forskolin reduced IL-1β-induced NO release and prevented IL-1β-induced mitochondrial impairment. Activation of AMPK increased IL-1β-induced NO production and the negative impact of IL-1β on mitochondrial respiration, whereas inhibition of AMPK had the opposite effects. NO is critically involved in the IL-1β-induced impairment of mitochondrial respiration in human OA chondrocytes. Increased intracellular cAMP or inhibition of AMPK prevented both IL-1β-induced NO release and mitochondrial dysfunction. View Full-Text
Keywords: osteoarthritis; NO synthase; Interleukin-1β; chondrocytes; mitochondrial dysfunction osteoarthritis; NO synthase; Interleukin-1β; chondrocytes; mitochondrial dysfunction
Show Figures

Figure 1

MDPI and ACS Style

Eitner, A.; Müller, S.; König, C.; Wilharm, A.; Raab, R.; Hofmann, G.O.; Kamradt, T.; Schaible, H.-G. Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes. Int. J. Mol. Sci. 2021, 22, 2477. https://doi.org/10.3390/ijms22052477

AMA Style

Eitner A, Müller S, König C, Wilharm A, Raab R, Hofmann GO, Kamradt T, Schaible H-G. Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes. International Journal of Molecular Sciences. 2021; 22(5):2477. https://doi.org/10.3390/ijms22052477

Chicago/Turabian Style

Eitner, Annett; Müller, Sylvia; König, Christian; Wilharm, Arne; Raab, Rebecca; Hofmann, Gunther O.; Kamradt, Thomas; Schaible, Hans-Georg. 2021. "Inhibition of Inducible Nitric Oxide Synthase Prevents IL-1β-Induced Mitochondrial Dysfunction in Human Chondrocytes" Int. J. Mol. Sci. 22, no. 5: 2477. https://doi.org/10.3390/ijms22052477

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop