Molecular and cellular assessment of dermal delayed-type hypersensitivity (DTH) responses is a useful approach for evaluating the mechanism of action (MOA) of immunomodulatory agents. In the present report, we characterized the delayed-type hypersensitivity response induced by keyhole limpet hemocyanin (KLH), and validated its utility by evaluating an immunomodulator, BIRB-796. Intradermal KLH challenge of the ear pinna following subcutaneous antigen sensitization resulted in a pronounced skin inflammation that peaked at 24-48h. At the molecular level, there was an activation of 3 mitogen-activated protein kinases (MAPKs: p38, JNK and ERK), an induction of the chemokines CCL2/JE, CXCL2/Mip-2, CXCL1/KC, CCL3/Mip-1alpha CCL4/Mip-1beta and CXCL10/IP-10, and expression of the cytokines IL-1beta and IL-10 in the ear parenchyma. Modulation of TNFalpha protein level was only detected in ex-vivo ear whole organ cultures (EWOC). Consistent with this inflammatory profile there was an infiltration of neutrophils and mononuclear cells into the ear parenchyma. BIRB-796, a potent allosteric p38 MAPK inhibitor attenuated the ear swelling response, which correlated with a reduced inflammatory profile. BIRB-796 inhibited p38 but not JNK or ERK kinase activation, decreased multiple chemokines which correlated with a decrease in the infiltration of neutrophils and macrophages; CD4 T cells were modesty reduced. Similarly, there was a decrease of levels of cytokines including IL-1beta, IL-10 and TNFalpha. These data support the utility of this model for evaluating immunomodulators on skin inflammation and suggest that modulation of p38 kinase may be of therapeutic value for the treatment of inflammatory skin conditions.

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乐备实是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
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