Dataset Information

Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis: an observational study design.

ABSTRACT: INTRODUCTION:Seldom cutaneous leishmaniasis (CL) may present as a lasting and active lesion(s), known as a non-healing form of CL (NHCL). Non-functional type 1 T helper (Th1) cells are assumed the most important factor in the outcome of the disease. The present study aims to assess some molecular defects that potentially contribute to Th1 impairment in NHCL. METHODS AND ANALYSIS:This prospective observational study will be implemented among five groups. The first and second groups comprise patients afflicted with non-healing and healing forms of CL, respectively. The third group consists of those recovered participants who have scars as a result of CL. Those participants who have never lived or travelled to endemic areas of leishmaniasis will comprise the fourth group. The fifth group comprises participants living in hyperendemic areas for leishmaniasis, although none of them have been afflicted by CL. The aim is to recruit 10 NHCL cases and 30 participants in each of the other groups. A leishmanin skin test (LST) will be performed to assess in vivo immunity against the Leishmania infection. The cytokine profile (interleukin (IL)-12p70, interferon (IFN)-?, C-X-C motif chemokine ligand (CXCL)-11 and IL-17a) of the isolated peripheral blood mononuclear cells (PBMCs) will be evaluated through ELISA. Real-time PCR will determine the C-X-C motif chemokine receptor (CXCR)-3 and IL-17a gene expression and expression of IL-12R?1 will be assessed by flow cytometry. Furthermore, IL-12B and IL-12RB1 mutation analysis will be performed. DISCUSSION:It is anticipated that the outcome of the current study will identify IL-12B and IL-12RB1 mutations, which lead to persistent lesions of CL. Furthermore, our expected results will reveal an association between NHCL and pro-inflammatory cytokines (IL-12p70, IFN-? IL-17a and CXCL-11), as well as CXCR-3 expression. ETHICS AND DISSEMINATION:This study has been approved by a local ethical committee. The final results will be disseminated through peer-reviewed journals and scientific conferences.

SUBMITTER: Moafi M

PROVIDER: S-EPMC5278291 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis: an observational study design.

Moafi Mohammad M Rezvan Hossein H Sherkat Roya R Taleban Roya R Asilian Ali A Zarkesh Esfahani Seyed Hamid SH Nilforoushzadeh Mohammad Ali MA Jaffary Fariba F Feizi Awat A

BMJ open 20170127 1

<h4>Introduction</h4>Seldom cutaneous leishmaniasis (CL) may present as a lasting and active lesion(s), known as a non-healing form of CL (NHCL). Non-functional type 1 T helper (Th1) cells are assumed the most important factor in the outcome of the disease. The present study aims to assess some molecular defects that potentially contribute to Th1 impairment in NHCL.<h4>Methods and analysis</h4>This prospective observational study will be implemented among five groups. The first and second groups ...[more]

PMID: 28132002

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Project description:The skin is one of the major immune organs producing large amounts of proinflammatory and inflammatory cytokines in response to internal or exogenous stimuli, inducing systemic inflammation in various internal organs. In recent years, organ damage associated with inflammatory skin diseases such as psoriasis and atopic dermatitis has received increasing attention, and vascular disorder such as arteriosclerosis is one of the serious complications of chronic inflammatory skin diseases. However, the detailed mechanism of arteriosclerosis in dermatitis and the role of cytokines have not been clarified so far. In the current study, using a spontaneous dermatitis model, we investigated the pathophysiology of arteriosclerosis and the treatment option for inflammatory skin conditions. We employed spontaneous dermatitis model mice overexpressing human caspase-1 in the epidermal keratinocyte (Kcasp1Tg). The thoracic and abdominal aorta was investigated histologically. GeneChip and RT-PCR analysis were performed to measure the changes in mRNA levels in the aorta. To elucidate the direct effect on the artery by major inflammatory cytokines, endothelial cells, vascular smooth muscle cells, and fibroblast cells were co-cultured with several cytokines, and mRNA expression levels were measured. In order to observe the efficacy of IL-17A/F in arteriosclerosis, cross-mating with IL-17A, IL-17F, and IL-17A/F deficient mice was performed. Finally, we also measured snap tension in the abdominal aorta in WT, Kcasp1Tg, and IL17A/F-deficient mice. Kcasp1Tg showed a decrease in the diameter of the abdominal aorta compared to wild-type mice. mRNA levels for six genes including Apol11b, Camp, Chil3, S100a8, S100a9, and Spta1 were increased in the abdominal aorta of Kcasp1Tg. Some of the above mRNA levels were also increased in the co-culture with major inflammatory cytokines, IL-17A/F, IL-1β, and TNF-α. Dermatitis improved and mRNA levels were partially ameliorated in Kcasp1Tg with IL-17A/F deletion. Arterial fragility was also evidenced in the inflammatory model, but arterial flexibility was revealed in the IL-17A/F deletion model. Severe dermatitis is closely related to secondary arteriosclerosis caused by the persistent release of inflammatory cytokines. The results also proved that treatment against IL-17A and F may ameliorate arteriosclerosis.

Dataset Information

Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis: an observational study design.

Publications

Evaluation of IL-12RB1, IL-12B, CXCR-3 and IL-17a expression in cases affected by a non-healing form of cutaneous leishmaniasis: an observational study design.

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