Growth factor and cytokine interactions in myogenesis. Part II. Expression of IGF binding proteins and protein kinases essential for myogenesis in mouse C2C12 myogenic cells exposed to TNF-α and IFN-γ

Abstract

The aim of the study was to examine potential interactions among IGF-I and proinflammatory cytokines, TNF-α and IFN-γ, in the regulation of local IGF-I bioavailability and cellular proteins mediating myogenic signals. We investigated levels of IGFBP-4, -5, -6, protein kinase Czeta (PKCζ), p38 and extracellular signal-regulated kinase (ERK1/2) in differentiating mouse C2C12 myoblasts. IGF-I significantly stimulated expression of IGFBP-5. TNF-α and IFN-γ attenuated the expression of IGFBP-4 and -6 under basal conditions and in the presence of IGF-I, and inhibited IGF-I-induced IGFBP-5 expression during 5-day myogenesis. TNF-α and IFN-γ markedly attenuated p38 expression in the presence of IGF-I on the 5th day of myogenesis. When combined with IGF-I the cytokines exerted opposite effects on the PKCζ level, i.e. TNF-α caused an increase, whereas IFN-γ reduced the cellular content of this kinase. Exposition of C2C12 myoblasts to IGF-I or cytokines led to the stimulation of ERK1/2 phosphorylation; however, both TNF-α and IFN-γ exerted an inhibitory effect on the activation of ERK1/2 in myoblasts cultured in the presence of IGF-I. We concluded as follows: i) TNF-α and IFN-γ present in the extracellular environment of differentiating C2C12 myoblasts can alter the local bioavailability of IGF-I by inhibiting the expression of IGFBP-4, -5, and -6, ii) the decrease in p38 expression and ERK1/2 phosphorylation in C2C12 myoblasts exposed to cytokines can lead to disturbances in IGF-I-regulated myogenesis.

Threonine deficiency decreased intestinal immunity and aggravated inflammation associated withNF-κBandtarget of rapamycinsignalling pathways in juvenile grass carp (Ctenopharyngodon idella) after infection withAeromonas hydrophila

“…In this study, we observed that threonine deficiency up-regulated IFN-γ mRNA levels in the intestines of juvenile grass carp. In mice, it was found that IFN-γ could enhance the PKCζ levels ( 86 ) , which could up-regulate IKKβ and IKKγ but ignore IKKα expression ( 87 ) . Hence, we hypothesised that threonine deficiency up-regulated the IFN-γ mRNA levels, partly resulting in increasing PKCζ levels, thus leading to the up-regulation of IKKβ and IKKγ (not IKKα ) in fish intestines.…”

Biological approaches to improve skeletal muscle healing after injury and disease

“…Several studies have shown that growth factors play a variety of roles during muscle regeneration (Gospodarowicz et al, 1976; Inselburg and Applebaum, 1978; Linkhart et al, 1981; Florini et al, 1986; Olson et al, 1986; Allen and Boxhorn, 1989; Jennische, 1989; Jin et al, 1990; Yablonka-Reuveni et al, 1990; Anderson et al, 1991; Grounds, 1991; Harrington et al, 1992; Doumit et al, 1993; McFarland et al, 1993; Barnard et al, 1994; Coleman et al, 1995; Johnson and Allen, 1995; Jones and Clemmons, 1995; Lefaucheur and Sebille, 1995; Zdanowicz et al, 1995; Chambers and McDermott, 1996; Engert et al, 1996; Florini et al, 1996; Papadakis et al, 1996; Quinn and Haugk, 1996; Floss et al, 1997; Kurek et al, 1997; Lamberts et al, 1997; Barton-Davis et al, 1998; Damon et al, 1998; Springer et al, 1998; Tatsumi et al, 1998; Keller et al, 1999; Gowdak et al, 2000; Sheehan et al, 2000; De Deyne et al, 2002; Musaro et al, 2004; Wieteska-Skrzeczynska et al, 2011a,b). Using a mouse model, Menetrey et al (2000) found that direct injections of insulin-like growth factor-1 (IGF-1), basic fibroblastic growth factor (bFGF), and, to a lesser extent, nerve growth factor (NGF), led to enhanced muscle healing in lacerated, contused, and strain-injured muscle at 2, 5, and 7 days after injury.…”

Interleukin-1β stimulates early myogenesis of mouse C2C12 myoblasts: the impact on myogenic regulatory factors, extracellular matrix components, IGF binding proteins and protein kinases

“…For example, in intact animals IL-1α elevated circulating IGFBP-1, effectively reducing IGF bioavailability (Benbassat et al 1999) pointing to the systemic mechanisms of cytokine catabolic effects. Regarding in vitro models, several studies reported the inhibition of myogenic effect of IGF-I (O'Connor et al 2008, Wieteska--Skrzeczyńska et al 2011, whereas others provided evidence for the contrary, i.e. synergistic interactions of cytokines with IGF-I system in controlling myoblast number and differentiation (Al-Shanti et al 2008).…”