Cytokine super-families affect adult stem cells : IL-6 and the skeletal muscle niche

[摘要] ENGLISH ABSTRACT: Background: IL-6 belongs to a cytokine super-family known to affect cell proliferation,although other family members are better characterized. Proliferation promotingfactors (IL-6) compete with differentiation promoting factors (myogenic regulatoryfactors: MyoD and myogenin) to affect cell cycle. Cell cycle progression is assessed bydetermining the proportion of cells shifting from arrest to chromatin synthesis andmitosis phases (G0/G1 and S and G2/M respectively).Methods: This study assessed the effects of IL-6 on cell cycle progression andproliferation vs. differentiation of C2C12 skeletal myoblasts. Physiological doses (10 or100 pg/ml) were compared to a high dose (10 ng/ml), with exposure lasting 48 hours(addition of IL-6 dose to proliferation medium at 0 and 24 hours). Acute signalingdownstream of the IL-6 gp130 receptor was assessed after the first exposure.Results: Propidium iodide analysis of nuclear material using flow cytometry indicatedshifts in forward scatter. Both Low and Medium doses shifted a greater proportion(p<0.05) of cells from G0/G1 to S and G2M phases at 24 hours and all doses resultedin the same shift (p<0.05) at the 48 hour time point. However, the High dosesignificantly (p<0.05) increased myogenin expression at the 48 hour time point.Microscopy indicated that confluence was prevented by low seeding density and didnot influence the result. Cells harvested at 5 minutes post stimulation indicated thatall doses significantly increased STAT3 phosphorylation. 10 minutes post stimulationthe High dose group sustained elevated levels of STAT3 phosphorylation.Conclusions: Low and medium doses of IL-6 increase proliferation in a musclesatellite cell line by activating cell division and allowing myoblasts to remain in theactive cell cycle. High doses of IL-6 increase differentiation by mediating upregulationof myogenic regulatory factors and this is thought to be due to prolonged STAT3activation. Physiological control of myoblast behaviour by cytokines is evident andsuch control would be influenced by the severity of the endogenous cytokineresponse to various stimuli.

[发布机构] Stellenbosch University