Dataset Information

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

ABSTRACT: In this study, we investigated the effects and mechanisms of the pro-inflammatory cytokines IL-1? and TNF-? 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-1?- and TNF-?-induced cell proliferation, and that the IL-1? effect also involved COX-2-derived PGs. Both cytokines modulated the release of the myokines myostatin, irisin, osteonectin, and IL-15. TNF-? 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-1? increased myogenin activity only in committed cells. Our data reveal a key role of IL-6 and COX-2-derived PGs in IL-1? and TNF-?-induced myoblast proliferation and support the link between TNF-? and IL-6 and the activation of MRFs. We concluded that IL-1? and TNF-? 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.

SUBMITTER: Alvarez AM

PROVIDER: S-EPMC7564831 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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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.

Alvarez Angela M AM DeOcesano-Pereira Carlos C Teixeira Catarina C Moreira Vanessa V

Cells 20200901 9

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 in ...[more]

PMID: 32882817

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Project description:Adipose tissue-derived stem cell (ADSC) transplantation has been shown to be effective for the management of severe liver disorders. Preactivation of ADSCs enhanced their therapeutic efficacy. However, these effects have not yet been examined in relation to cholestatic liver injury. In the present study, a cholestatic liver injury model was established by bile duct ligation (BDL) in male C57BL/6 mice. Human ADSCs (hADSCs) with or without tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β) pretreatment were administrated into the mice via tail vein injections. The efficacy of hADSCs on BDL-induced liver injury was assessed by histological staining, real-time quantitative PCR (RT-qPCR), Western blot, and enzyme-linked immune sorbent assay (ELISA). In vitro, the effects of hADSC conditioned medium on the activation of hepatic stellate cells (HSCs) were investigated. Small interfering RNA (siRNA) was used to knock down cyclooxygenase-2 (COX-2) in hADSCs. TNF-α/IL-1β preconditioning could downregulate immunogenic gene expression and enhance the engraftment efficiency of hADSCs. Compared to control hADSCs (C-hADSCs), TNF-α/IL-1β-pretreated hADSCs (P-hADSCs) significantly alleviated BDL-induced liver injury, as demonstrated by reduced hepatic cell death, attenuated infiltration of Ly6G + neutrophils, and decreased expression of pro-inflammatory cytokines TNF-α, IL-1β, C-X-C motif chemokine ligand 1 (CXCL1), and C-X-C motif chemokine ligand 2 (CXCL2). Moreover, P-hADSCs significantly delayed the development of BDL-induced liver fibrosis. In vitro, conditioned medium from P-hADSCs significantly inhibited HSC activation compared to that from C-hADSCs. Mechanistically, TNF-α/IL-1β upregulated COX-2 expression and increased prostaglandin E2 (PGE2) secretion. The blockage of COX-2 by siRNA transfection reversed the benefits of P-hADSCs for PGE2 production, HSC activation, and liver fibrosis progression. In conclusion, our results suggest that TNF-α/IL-1β pretreatment enhances the efficacy of hADSCs in mice with cholestatic liver injury, partially through the COX-2/PGE2 pathway.

Dataset Information

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

Publications

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.

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