Interleukin-17A promotes arginase-1 production and 2,4-dinitrochlorobenzene-induced acute hyperinflammation in human papillomavirus E7 oncoprotein-expressing skin

Tran, Le Son, Mittal, Deepak, Mattarollo, Stephen R. and Frazer, Ian H. (2015) Interleukin-17A promotes arginase-1 production and 2,4-dinitrochlorobenzene-induced acute hyperinflammation in human papillomavirus E7 oncoprotein-expressing skin. Journal of Innate Immunity, 7 4: 392-404. doi:10.1159/000374115


Author Tran, Le Son
Mittal, Deepak
Mattarollo, Stephen R.
Frazer, Ian H.
Title Interleukin-17A promotes arginase-1 production and 2,4-dinitrochlorobenzene-induced acute hyperinflammation in human papillomavirus E7 oncoprotein-expressing skin
Journal name Journal of Innate Immunity   Check publisher's open access policy
ISSN 1662-811X
1662-8128
Publication date 2015-06
Year available 2015
Sub-type Article (original research)
DOI 10.1159/000374115
Volume 7
Issue 4
Start page 392
End page 404
Total pages 13
Place of publication Basel, Switzerland
Publisher S. Karger AG
Collection year 2016
Language eng
Abstract Human papillomaviruses (HPVs) have evoked numerous mechanisms to subvert host innate immunity and establish a local immunosuppressive environment to facilitate persistent virus infection. Topical application of 2,4-dinitrochlorobenzene (DNCB) was speculated to overcome this immunosuppressive environment and was employed in the immunotherapy of HPV-associated lesions. We have previously shown that DNCB treatment of skin expressing HPV16.E7 protein, the major oncogenic protein expressed in HPV-associated premalignant cervical epithelium, results in a hyperinflammatory response, with an associated induction of Th2 cytokines and infiltration of myeloid cells producing arginase-1, which also contributes to the hyperinflammation. However, the molecular mechanisms underlying arginase-1 induction and arginase-mediated hyperinflammation in K14.E7 skin have not been elucidated. Here, we show that HPV16.E7 protein expression as a transgene in skin is associated with enhanced IL-17A production by macrophages exposed to DNCB. Interestingly, induction of arginase-1 by DNCB is not seen in K14.E7 animals unable to express IL-17A. Further, blockade of either IL-17A or arginase activity alleviates DNCB-induced hyperinflammation through reduced recruitment of neutrophils, as a consequence of decreased CXCL1 and CXCL5 chemokine production. Thus, our findings suggest that increased IL-17A expression by macrophages in E7-expressing skin exposed to DNCB promotes arginase-1 induction and contributes directly to the observed hyperinflammation.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
UQ Diamantina Institute Publications
 
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Created: Thu, 12 Mar 2015, 14:57:32 EST by Dr Stephen Mattarollo on behalf of UQ Diamantina Institute