Expression of IL-10-triggered STAT3-dependent IL-4R α is required for induction of arginase 1 in visceral leishmaniasis

Biswas, Arunima ; Bhattacharya, Arijit ; Kar, Susanta ; Das, Pijush K. (2011) Expression of IL-10-triggered STAT3-dependent IL-4R α is required for induction of arginase 1 in visceral leishmaniasis European Journal of Immunology, 41 (4). pp. 992-1003. ISSN 0014-2980

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Official URL: http://onlinelibrary.wiley.com/doi/10.1002/eji.201...

Related URL: http://dx.doi.org/10.1002/eji.201040940

Abstract

Although enhanced macrophage-specific arginase activity is directly related to increased parasite burden in cutaneous leishmaniasis (CL), the regulation and precise role of arginase in the disease outcome of visceral leishmaniasis (VL) has yet to be explored. As in CL, BALB/c mice infected with Leishmania donovani showed increased levels of arginase in acute infection. Arginase 1 is the major isoform associated with infection and while the IL-4-induced arginase pathway is operative in CL, IL-10 plays a crucial role in modulating arginase activity in VL, although a synergism with IL-4 is required. IL-10, in combination with IL-4, regulated both in vivo and ex vivo arginase 1 induction in a STAT6 and C/EBPβ-dependent fashion. Further investigation toward the cause of such synergism suggests that induction of a STAT3-dependent IL-10-mediated cascade in VL triggers the expression and surface localization of the IL-4 receptor alpha (IL-4Rα) which, in turn, enhances IL-4 responsiveness toward STAT6 and C/EBPβ-dependent signaling for arginase 1. This could also offer a mechanistic explanation for the fact that, in spite of the low level of IL-4 in VL, enhanced IL-4-R αexpression by IL-10 might markedly amplify IL-4-mediated arginase 1 signaling and provide a possible mechanism for synergistic induction of arginase 1.

Item Type:Article
Source:Copyright of this article belongs to John Wiley and Sons.
Keywords:Arginase 1; IL-4; IL-10; IL-4 Receptor; Visceral Leishmaniasis
ID Code:93778
Deposited On:27 Jun 2012 11:10
Last Modified:27 Jun 2012 11:10

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