Heterotrimeric complex of p38 MAPK, PKCδ, and TIRAP is required for AP1 mediated inflammatory response

Publication date: July 2017
Source:International Immunopharmacology, Volume 48
Author(s): Mirza S. Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M. Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes.There is a significant increase in active p38 mitogen-activated protein kinase (p38MAK) immediately after lipopolysaccharide (LPS) stimulation, which results in the activation of AP-1 transcription factor and expression of proinflammatory cytokines, IL-12 and IL-23. We studied the novel mechanism of p38 MAPK activation through the formation of a heterotrimeric complex of Protein kinase C delta type (PKCδ), Toll-Interleukin 1 Receptor (TIR) Domain Containing Adaptor Protein (TIRAP), and p38 proteins. TIRAP serves as an adaptor molecule which brings PKCδ and p38 in close proximity. The complex facilitates the activation of p38MAPK by PKCδ.Therefore, we propose that disruption of the heterotrimeric complex may be a good strategy to dampen the inflammatory response. Structure-based design of small molecules or peptides targetting PKCδ-TIRAP or TIRAP-p38 interfaces would be beneficial for therapy in AP1 mediated inflammatory diseases.



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Inside front cover

Publication date: June 2017
Source:International Immunopharmacology, Volume 47





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Posters Presented at the 20th Joint Meeting of the International Society of Dermatopathology, March 1-2, 2017, Hilton Orlando Lake Buena Vista in the Walt Disney World Resort, Lake Buena Vista, Florida, USA.

No abstract available

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Specific Skin Lesions of Sarcoidosis Located at Venipuncture Points for Blood Sample Collection.

It has been suggested that the predilection of sarcoidosis to affect scars is due to the presence of antigens or foreign bodies that can serve as a stimulus for granuloma formation. Several patients with sarcoidosis-specific skin lesions in venous puncture sites have been reported. However, in these patients the pathogenesis of the cutaneous lesions is not clear because the presence of foreign bodies is not to be expected. Our objective was to describe 3 patients who developed specific lesions of sarcoidosis in areas of venipuncture and to discuss their possible pathogenesis. The database of the Sarcoid Clinic of Bellvitge Hospital (an 800-bed university referral center providing tertiary care to approximately 1 million people in Barcelona, Spain) was reviewed to detect those patients with specific cutaneous lesions of systemic sarcoidosis in areas of venipuncture. Three patients with biopsy-proven specific cutaneous lesions of systemic sarcoidosis in areas of venipuncture for blood collection were detected (3 women, mean age 56 years). In one case, the histopathological image shows the hypothetical path of a needle through the skin. In 2 cases, an amorphous birefringent material was detected under polarized light. This material was consistent with silicone. In patients who are developing sarcoidosis, the smallest amount of oil used as lubricant in the needle for sample blood collection may induce the formation of granulomas. In addition to exploring scars, it is advisable to explore the cubital folds to detect specific cutaneous lesions of sarcoidosis. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Tuberculosis of Lip-An Unusual Presentation.

No abstract available

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Utility of Skin Biopsy in a Case of Progressive Myoclonic Epilepsy.

No abstract available

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Abstracts Presented at the 20th Joint Meeting of the International Society of Dermatopathology, March 1-2, 2017, Hilton Orlando Lake Buena Vista in the Walt Disney World Resort, Lake Buena Vista, Florida, USA.

No abstract available

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