Abstract
The glycoprotein 130 (gp130) dependent family of cytokines comprises interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1) and oncostatin M (OSM). These cytokines share the membrane gp130 as a common signal transducer. Recently, it was demonstrated that IL-6 promotes, whereas LIF inhibits fetal lung branching. Thus, in this study, the effects on fetal lung morphogenesis of the other classical members of the gp130-type cytokines (IL-11, CLC, CNTF, CT-1 and OSM) were investigated. We also provide the first description of these cytokines and their common gp130 receptor protein expression patterns during rat lung development. Fetal rat lung explants were cultured in vitro with increasing concentrations of IL-11, CLC, CNTF, CT-1 and OSM. Treated lung explants were morphometrically analyzed and assessed for MAPK, PI3K/AKT and STAT3 signaling modifications. IL-11, which similarly to IL-6 acts through a gp130 homodimer receptor, significantly stimulated lung growth via p38 phosphorylation. On the other hand, CLC, CNTF, CT-1 and OSM, whose receptors are gp130 heterodimers, inhibited lung growth acting in different signal-transducing pathways. Thus, the present study demonstrated that although cytokines of the gp130 family share a common signal transducer, there are specific biological activities for each cytokine on lung development. Indeed, cytokine signaling through gp130 homodimers stimulate, whereas cytokine signaling through gp130 heterodimers inhibit lung branching.
Highlights
Normal lung development is dependent on tightly regulated signaling networks, triggered by both its classically known effectors, such as growth factors, extracellular matrix molecules and hormones, and by its recently implicated regulatory factors like inflammatory cytokines [1,2,3,4].The glycoprotein 130 dependent family of cytokines or interleukin 6 (IL-6) family of cytokines is quite a large group of structurally related cytokines that includes IL-6, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), and oncostatin M (OSM) [5,6]
Spatio-temporal protein expression pattern of IL-11, CLC, CNTF, CT-1, OSM and gp130 receptor were assessed in the developing lung at five gestational ages, 13.5, 15.5, 17.5, 19.5 and 21.5 dpc and in the adult lung tissue
Immunohistochemistry revealed that all these cytokines and their common gp130 receptor are expressed throughout all studied gestational ages in the fetal lung (Figures 1, 2, 3, 4, 5, 6)
Summary
Normal lung development is dependent on tightly regulated signaling networks, triggered by both its classically known effectors, such as growth factors, extracellular matrix molecules and hormones, and by its recently implicated regulatory factors like inflammatory cytokines [1,2,3,4].The glycoprotein 130 (gp130) dependent family of cytokines or interleukin 6 (IL-6) family of cytokines is quite a large group of structurally related cytokines that includes IL-6, IL-11, leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), and oncostatin M (OSM) [5,6]. Other family members have recently emerged (IL-27 and neuropoietin), it is likely that the currently defined gp130 cytokine family is not complete [5,7,8]. These small proteins are grouped in same family, since all signal through a common signal transducing receptor chain, the gp130. The multimeric receptor complex for gp130 family of cytokines consists of (i) gp130 homodimers with a ligand-specific a chain for IL-6 and IL-11; (ii) gp130 heterodimers (gp130/LIFR and gp130/OSMR) without specific a chain for LIF and OSM; or (iii) gp130 heterodimers with a ligand-specific a chain (CNTFRa) for CNTF and CLC or a chain-like for CT-1 [5,6,7]. The a chain recruited by CT-1 has not been characterized [5]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
