Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8
Summary: Antimicrobial peptides (AMPs) are the body’s natural innate immune defense against a spectrum of pathogens and can also modulate cell proliferation, chemotaxis, angiogenesis, wound healing, and immune cell activity. Harnessing these diverse functions for prophylactic use is contingent upon...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124719314123 |
| _version_ | 1819228355408429056 |
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| author | Tanay Bhatt Aishwarya Bhosale Bhavya Bajantri Mruthyunjaya Swamy Mathapathi Abrar Rizvi Giorgio Scita Amitabha Majumdar Colin Jamora |
| author_facet | Tanay Bhatt Aishwarya Bhosale Bhavya Bajantri Mruthyunjaya Swamy Mathapathi Abrar Rizvi Giorgio Scita Amitabha Majumdar Colin Jamora |
| author_sort | Tanay Bhatt |
| collection | DOAJ |
| description | Summary: Antimicrobial peptides (AMPs) are the body’s natural innate immune defense against a spectrum of pathogens and can also modulate cell proliferation, chemotaxis, angiogenesis, wound healing, and immune cell activity. Harnessing these diverse functions for prophylactic use is contingent upon understanding the regulatory mechanisms governing their unconventional secretion from cells. Analysis of the secretion of S100A7 (Psoriasin), an abundant AMP stored in differentiated keratinocytes of the skin, has revealed an unexpected biphasic secretory response to bacterial exposure. The core components regulating S100A7 secretion are NFκB/p38MAPK, caspase-1, and interleukin (IL)-1α. The initial activation of this core machinery is mediated by Toll-like receptor signaling, whereas the chronic response is mediated by Caspase-8 downregulation. Interestingly, there is a concomitant downregulation of Caspase-8 in inflammatory skin diseases wherein S100A7 is constitutively released. These results highlight the potential of targeting these components to control the release of AMPs from the skin in both homeostatic and disease conditions. : The global explosion of antibiotic-resistant microorganisms has spurred interest in alternative strategies to combat these “superbugs.” Antimicrobial peptides (AMPs) have emerged as a promising solution. Bhatt et al. show downregulation of epidermal caspase-8 can mediate sustained release of AMPs from the skin and provide an effective defense against infection. keywords: caspase, antimicrobial peptides, skin, TLR, IL-1, NFkB, psoriasis, antibiotic resistance |
| first_indexed | 2024-12-23T10:55:58Z |
| format | Article |
| id | doaj.art-cee25ff0a57f4071bea6cdb17e195343 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-23T10:55:58Z |
| publishDate | 2019-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-cee25ff0a57f4071bea6cdb17e1953432022-12-21T17:49:47ZengElsevierCell Reports2211-12472019-11-0129925462555.e4Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8Tanay Bhatt0Aishwarya Bhosale1Bhavya Bajantri2Mruthyunjaya Swamy Mathapathi3Abrar Rizvi4Giorgio Scita5Amitabha Majumdar6Colin Jamora7IFOM-inStem Joint Research Laboratory, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065, India; National Centre for Biological Sciences (TIFR), Bangalore, Karnataka 560065, IndiaIFOM-inStem Joint Research Laboratory, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065, IndiaIFOM-inStem Joint Research Laboratory, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065, IndiaUnilever R&D Bangalore, Karnataka 560066, IndiaIFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy; Department of Oncology and Hemato-oncology, School of Medicine, University of Milan, 20122 Milan, ItalyIFOM, FIRC Institute of Molecular Oncology, 20139 Milan, Italy; Department of Oncology and Hemato-oncology, School of Medicine, University of Milan, 20122 Milan, ItalyUnilever R&D Bangalore, Karnataka 560066, India; Corresponding authorIFOM-inStem Joint Research Laboratory, Institute for Stem Cell Science and Regenerative Medicine (inStem), Bangalore, Karnataka 560065, India; Corresponding authorSummary: Antimicrobial peptides (AMPs) are the body’s natural innate immune defense against a spectrum of pathogens and can also modulate cell proliferation, chemotaxis, angiogenesis, wound healing, and immune cell activity. Harnessing these diverse functions for prophylactic use is contingent upon understanding the regulatory mechanisms governing their unconventional secretion from cells. Analysis of the secretion of S100A7 (Psoriasin), an abundant AMP stored in differentiated keratinocytes of the skin, has revealed an unexpected biphasic secretory response to bacterial exposure. The core components regulating S100A7 secretion are NFκB/p38MAPK, caspase-1, and interleukin (IL)-1α. The initial activation of this core machinery is mediated by Toll-like receptor signaling, whereas the chronic response is mediated by Caspase-8 downregulation. Interestingly, there is a concomitant downregulation of Caspase-8 in inflammatory skin diseases wherein S100A7 is constitutively released. These results highlight the potential of targeting these components to control the release of AMPs from the skin in both homeostatic and disease conditions. : The global explosion of antibiotic-resistant microorganisms has spurred interest in alternative strategies to combat these “superbugs.” Antimicrobial peptides (AMPs) have emerged as a promising solution. Bhatt et al. show downregulation of epidermal caspase-8 can mediate sustained release of AMPs from the skin and provide an effective defense against infection. keywords: caspase, antimicrobial peptides, skin, TLR, IL-1, NFkB, psoriasis, antibiotic resistancehttp://www.sciencedirect.com/science/article/pii/S2211124719314123 |
| spellingShingle | Tanay Bhatt Aishwarya Bhosale Bhavya Bajantri Mruthyunjaya Swamy Mathapathi Abrar Rizvi Giorgio Scita Amitabha Majumdar Colin Jamora Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8 Cell Reports |
| title | Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8 |
| title_full | Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8 |
| title_fullStr | Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8 |
| title_full_unstemmed | Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8 |
| title_short | Sustained Secretion of the Antimicrobial Peptide S100A7 Is Dependent on the Downregulation of Caspase-8 |
| title_sort | sustained secretion of the antimicrobial peptide s100a7 is dependent on the downregulation of caspase 8 |
| url | http://www.sciencedirect.com/science/article/pii/S2211124719314123 |
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