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Sustained Secretion of the Antimicrobial Peptide S100A7 Is Mediated by the Wound Healing Machinery

44 Pages Posted: 26 Feb 2019 Sneak Peek Status: Review Complete

See all articles by Tanay Bhatt

Tanay Bhatt

inStem-Bangalore - IFOM-inStem Joint Research Laboratory; Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Sciences (TIFR)

Mruthyunjaya MS

Unilever, Unilever R&D Bangalore, Human Microbiome

Aishwarya Bhosale

inStem-Bangalore - IFOM-inStem Joint Research Laboratory

Bhavya Bajantri

inStem-Bangalore - IFOM-inStem Joint Research Laboratory

Abrar Rizvi

Fondazione Istituto FIRC di Oncologia Molecolare - IFOM

Giorgio Scita

Fondazione Istituto FIRC di Oncologia Molecolare - IFOM

Amitabha Majumdar

Unilever, Unilever R&D Bangalore, Human Microbiome

Colin Jamora

inStem-Bangalore - IFOM-inStem Joint Research Laboratory

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Abstract

Antimicrobial peptides (AMPs) are the body’s natural innate immune defense against a spectrum of pathogenic insults and provide an attractive strategy towards combating the growing problem of antibiotic resistant microorganisms. The prophylactic use of AMPs is contingent upon understanding the regulatory mechanisms governing the release of AMPs from intracellular stores, which occurs via the non-conventional secretory pathway. Analysis of S100A7 (Psoriasin), an abundant AMP in the skin, from its endogenous stores within differentiated keratinocytes has revealed an unexpected biphasic secretory response to bacterial exposure. The core components regulating S100A7 secretion are NFκB/p38MAPK, caspase-1 and IL-1α. The early activation of this core machinery is mediated by toll-like receptor signaling, whereas the chronic response is regulated by the wound-healing machinery mediated by Caspase-8 downregulation. Interestingly, in inflammatory skin diseases in which S100A7 is excessively released, there is a concomitant downregulation of caspase-8, indicating that these pathological scenarios are commandeering the normal wound healing response. These results highlight the potential benefits of targeting intracellular wound healing pathways as a means of exerting control over the release of AMPs from the skin in both homeostatic and disease conditions.

Suggested Citation

Bhatt, Tanay and MS, Mruthyunjaya and Bhosale, Aishwarya and Bajantri, Bhavya and Rizvi, Abrar and Scita, Giorgio and Majumdar, Amitabha and Jamora, Colin, Sustained Secretion of the Antimicrobial Peptide S100A7 Is Mediated by the Wound Healing Machinery (January 25, 2019). Available at SSRN: https://ssrn.com/abstract=3322364 or http://dx.doi.org/10.2139/ssrn.3322364
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Tanay Bhatt

inStem-Bangalore - IFOM-inStem Joint Research Laboratory

Bangalore
India

Tata Institute of Fundamental Research (TIFR) - National Centre for Biological Sciences (TIFR)

Bangalore
India

Mruthyunjaya MS

Unilever, Unilever R&D Bangalore, Human Microbiome

Bangalore
India

Aishwarya Bhosale

inStem-Bangalore - IFOM-inStem Joint Research Laboratory

Bangalore
India

Bhavya Bajantri

inStem-Bangalore - IFOM-inStem Joint Research Laboratory

Bangalore
India

Abrar Rizvi

Fondazione Istituto FIRC di Oncologia Molecolare - IFOM

Milan
Italy

Giorgio Scita

Fondazione Istituto FIRC di Oncologia Molecolare - IFOM

Milan
Italy

Amitabha Majumdar

Unilever, Unilever R&D Bangalore, Human Microbiome ( email )

Bangalore
India

Colin Jamora (Contact Author)

inStem-Bangalore - IFOM-inStem Joint Research Laboratory ( email )

Bangalore
India

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