Ential for the elimination of intracellular pathogens such as Leishmania and Salmonella (9). In contrast, exposure towards the Th2 cytokines IL-4 and IL-13 promotes the differentiation of alternatively activated macrophages (AAMacs) that are defined by IL-1 Proteins Purity & Documentation the2009 Nair et al. This article is distributed beneath the terms of an Attribution oncommercial hare Alike o Mirror Web pages license for the very first six months soon after the publication date (see http://www.jem.org/misc/terms.shtml). Immediately after six months it really is readily available under a Inventive Commons License (Attribution oncommercial hare Alike 3.0 Unported license, as described at http://creativecommons .org/licenses/by-nc-sa/3.0/).The Rockefeller University Press 30.00 J. Exp. Med. Vol. 206 No. 4 937-952 www.jem.org/cgi/doi/10.1084/jem.expression of a panel of signature genes including Arginase 1, chitinase-like molecules (Ym1/2 and AMCase), and resistinlike molecule (RELM) (103). Although the Serine/Threonine Kinase Proteins web recruitment of AAMacs is usually a characteristic feature of a wide range of inflammatory situations related with parasite infection, allergy, diabetes, and cancer (7, 147), their possible roles in influencing the improvement, severity, or resolution of inflammatory responses have remained controversial. By way of example, quite a few advantageous functions for AAMacs have been proposed, which incorporate enhancing host defense against parasite infection (14, 18), the amelioration of diabetes by means of the regulation of nutrient homeostasis (16), and promotion of tissue repair immediately after injury (10, 19, 20). In contrast, tumor-associated AAMacs and these which can be recruited in Th2 cytokine-mediated allergic responses have already been implicated within the exacerbation of illness (7, 17, 213). The putative pleiotropic functions of AAMacs may perhaps relate to heterogeneity in expression of signature molecules such as Arginase 1, chitinase-like molecules, and RELM-; having said that, to date there has been no systematic analysis in the roles of these molecules within the regulation of inflammatory responses. In this study, we examined the functions of RELM- in Th2 cytokine-mediated lung inflammation. RELM- belongs to a family of small cysteine-rich secreted proteins that are conserved in mammals (246) and it exhibits a broad pattern of expression in hematopoietic and nonhematopoietic cells (11, 246). Elevated expression of RELM- in mouse models of pulmonary inflammation (24, 279) and improved expression from the connected human protein resistin in inflammatory diseases in individuals (30) implicate a putative function in influencing innate and adaptive immune responses. Nevertheless, earlier studies have identified contrasting effects of RELM- in regulating inflammation. Constant having a function in promoting pulmonary inflammation, in vitro research showed that recombinant RELM- (rRELM-) could drive proliferation and growth aspect expression in lung fibroblast cell lines (31, 32). In contrast, rRELM- was reported to antagonize the effects of nerve development issue, a protein related using the exacerbation of allergic pulmonary responses (33), suggesting that RELM- might negatively regulate Th2 cytokine-mediated inflammation inside the lung. To investigate these paradoxical findings, we employed mice deficient in RELM- (Retnla/) in an in vivo model of Th2 cytokine-dependent pulmonary inflammation and fibrosis (19, 27). In response to challenge with eggs in the helminth parasite Schistosoma mansoni (Sm), Retnla/ mice exhibited more serious pulmonary inflammation and exacerbated egg-induced granuloma formati.
