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Article

IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved

1
Centre of Excellence in New Target Discovery (CENTD), Butantan Institute, São Paulo, SP 05503-900, Brazil
2
Pharmacology Department, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP 04044-020, Brazil
3
Pharmacology Laboratory, Butantan Institute, São Paulo, SP 05503-900, Brazil
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2020, 9(9), 2005; https://doi.org/10.3390/cells9092005
Received: 29 July 2020 / Revised: 20 August 2020 / Accepted: 22 August 2020 / Published: 1 September 2020
(This article belongs to the Section Cellular Immunology)
In this study, we investigated the effects and mechanisms of the pro-inflammatory cytokines IL-1β and TNF-α on the proliferation and commitment phases of myoblast differentiation. C2C12 mouse myoblast cells were cultured to reach a proliferated or committed status and were incubated with these cytokines for the evaluation of cell proliferation, cyclooxygenase 2 (COX-2) expression, release of prostaglandins (PGs) and myokines, and activation of myogenic regulatory factors (MRFs). We found that inhibition of the IL-6 receptor reduced IL-1β- and TNF-α-induced cell proliferation, and that the IL-1β effect also involved COX-2-derived PGs. Both cytokines modulated the release of the myokines myostatin, irisin, osteonectin, and IL-15. TNF-α and IL-6 reduced the activity of Pax7 in proliferated cells and reduced MyoD and myogenin activity at both proliferative and commitment stages. Otherwise, IL-1β increased myogenin activity only in committed cells. Our data reveal a key role of IL-6 and COX-2-derived PGs in IL-1β and TNF-α-induced myoblast proliferation and support the link between TNF-α and IL-6 and the activation of MRFs. We concluded that IL-1β and TNF-α induce similar effects at the initial stages of muscle regeneration but found critical differences between their effects with the progression of the process, bringing new insights into inflammatory signalling in skeletal muscle regeneration. View Full-Text
Keywords: myoblast; inflammation; cytokines; proliferation; myogenesis; muscle regeneration myoblast; inflammation; cytokines; proliferation; myogenesis; muscle regeneration
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MDPI and ACS Style

Alvarez, A.M.; DeOcesano-Pereira, C.; Teixeira, C.; Moreira, V. IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved. Cells 2020, 9, 2005. https://doi.org/10.3390/cells9092005

AMA Style

Alvarez AM, DeOcesano-Pereira C, Teixeira C, Moreira V. IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved. Cells. 2020; 9(9):2005. https://doi.org/10.3390/cells9092005

Chicago/Turabian Style

Alvarez, Angela M., Carlos DeOcesano-Pereira, Catarina Teixeira, and Vanessa Moreira. 2020. "IL-1β and TNF-α Modulation of Proliferated and Committed Myoblasts: IL-6 and COX-2-Derived Prostaglandins as Key Actors in the Mechanisms Involved" Cells 9, no. 9: 2005. https://doi.org/10.3390/cells9092005

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