Leukotriene B₄-leukotriene B₄ receptor axis promotes oxazolone-induced contact dermatitis by directing skin homing of neutrophils and CD8⁺ T cells
| Autor: | Jiaoyan, Lv, Linlin, Zou, Lina, Zhao, Wei, Yang, Yingluo, Xiong, Bingji, Li, Rui, He |
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| Rok vydání: | 2014 |
| Předmět: |
Neutrophils
Chemokine CXCL1 Chemokine CXCL2 Interleukin-1beta Receptors Leukotriene B4 CD8-Positive T-Lymphocytes Dermatitis Contact Leukotriene B4 Glycols Interferon-gamma Mice Leucine Animals Skin Epoxide Hydrolases Inflammation Mice Knockout Arachidonate 5-Lipoxygenase integumentary system Oxazolone Original Articles respiratory system Mice Inbred C57BL lipids (amino acids peptides and proteins) Female Fatty Alcohols |
| Zdroj: | Immunology. 146(1) |
| ISSN: | 1365-2567 |
| Popis: | Leukotriene B4 (LTB4 ) is a lipid mediator that is rapidly generated in inflammatory sites, and its functional receptor, BLT1, is mostly expressed on immune cells. Contact dermatitis is a common inflammatory skin disease characterized by skin oedema and abundant inflammatory infiltrates, primarily including neutrophils and CD8(+) T cells. The role of the LTB4 -BLT1 axis in contact dermatitis remains largely unknown. In this study, we found up-regulated gene expression of 5-lipoxygenase and leukotriene A4 hydrolase, two critical enzymes for LTB4 synthesis, BLT1 and elevated LTB4 levels in skin lesions of oxazolone (OXA)-induced contact dermatitis. BLT1 deficiency or blockade of LTB4 and BLT1 by the antagonists, bestatin and U-75302, respectively, in the elicitation phase caused significant decreases in ear swelling and skin-infiltrating neutrophils and CD8(+) T cells, which was accompanied by significantly reduced skin expression of CXCL1, CXCL2, interferon-γ and interleukin-1β. Furthermore, neutrophil depletion during the elicitation phase of OXA-induced contact dermatitis also caused significant decreases in ear swelling and CD8(+) T-cell infiltration accompanied by significantly decreased LTB4 synthesis and gene expression of CXCL2, interferon-γ and interleukin-1β. Importantly, subcutaneous injection of exogenous LTB4 restored the skin infiltration of CD8(+) T cells in neutrophil-depleted mice following OXA challenge. Collectively, our results demonstrate that the LTB4 -BLT1 axis contributes to OXA-induced contact dermatitis by mediating skin recruitment of neutrophils, which are a major source of LTB4 that sequentially direct CD8(+) T-cell homing to OXA-challenged skin. Hence, LTB4 and BLT1 could be potential therapeutic targets for the treatment of contact dermatitis. |
| Databáze: | OpenAIRE |
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