title: Interleukin-4 blocks proliferation of retinal progenitor cells and increases rod photoreceptor differentiation through distinct signaling pathways.
abstract: Interleukin-4 (IL-4), an anti-inflammatory cytokine, has been related to the differentiation of the rodent retina in vitro, but constitutive presence of either IL-4 or of IL-4 receptor in the retina has not been reported. In this work we examined the expression of IL-4 and its specific receptor alpha subunit (IL-4Ralpha). IL-4Ralpha is expressed both in neural retina and non-neural ocular tissue, while IL-4 was found mainly in non-neural tissue. We characterized a novel trophic effect of IL-4 upon the retina. We showed that IL-4 can inhibit the proliferation of retinal cells (approximately 40%) through the cAMP-PKA pathway and associated with a reduction of cyclin D1 and increase of p27(kip1). IL-4 also promotes the differentiation of rod photoreceptors. Activation of tyrosine kinases, protein kinase C, and mitogen-activated kinases of the Erk family were required for IL-4-induced rod photoreceptor differentiation, independent of the release of other trophic factors in culture. Taken together, our results show, for the first time, that IL-4 directly modulates proliferation of retinal cells and rod photoreceptor differentiation, through distinct signaling pathways.
authors: Programa de Neurobiologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bl G, Cidade Universitária, 21949-900, Rio de Janeiro, RJ, Brazil.
authors: Ana Gabriela Ledo Santos
authors: AG
authors: da Silva
authors: Paula
authors: P
authors: Campello-Costa
authors: Rafael
authors: R
authors: Linden
authors: Alfred
authors: A
authors: Sholl-Franco
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011494:Protein Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D012160:Retina / Q000166:cytology* / Q000187:drug effects; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects*; D012243:Rhodopsin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013234:Stem Cells / Q000187:drug effects*; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D015703:Antigens, CD; D000242:Cyclic AMP; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D015847:Interleukin-4; D011494:Protein Kinases; D011956:Receptors, Cell Surface; D012243:Rhodopsin; D013936:Thymidine; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit