Cortisol biosynthesis in the human ocular surface innate immune response.

Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in O...

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Autores principales:	Radhika Susarla, Lei Liu, Elizabeth A Walker, Iwona J Bujalska, Jawaher Alsalem, Geraint P Williams, Sreekanth Sreekantam, Angela E Taylor, Mohammad Tallouzi, H Susan Southworth, Philip I Murray, Graham R Wallace, Saaeha Rauz
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2bd508f07b346feb6cb34bfdf15e08a
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spelling	oai:doaj.org-article:d2bd508f07b346feb6cb34bfdf15e08a2021-11-18T08:23:12ZCortisol biosynthesis in the human ocular surface innate immune response.1932-620310.1371/journal.pone.0094913https://doaj.org/article/d2bd508f07b346feb6cb34bfdf15e08a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24736562/?tool=EBIhttps://doaj.org/toc/1932-6203Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in OcS defense, remains unresolved. We found that primary human corneal epithelial cells (PHCEC), fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was independent of Toll-like receptor (TLR) activation. While PolyI∶C induced maximal cytokine and chemokine production from both PHCEC (IFNγ, CCL2, CCL3, and (CCL4), IL6, CXCL10, CCL5, TNFα) and PHKF (CCL2, IL-6, CXCL10, CCL5), only PHKF cytokines were inhibited by GCs. Both Poly I∶C and LPS challenged-corneal cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1 11β-HSD1 activity (30 and 40% respectively). These data were supported by clinical studies demonstrating reduced human tear film cortisol∶cortisone ratios (a biomarker of local 11β-HSD1 activity) in pseudomonas keratitis (1∶2.9) versus healthy controls (1∶1.3; p<0.05). This contrasted with putative TLR3-mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where an increase in cortisol∶cortisone ratio was observed (113.8∶1; p<0.05). In summary, cortisol biosynthesis in human corneal cells is independent of TLR activation and is likely to afford immunoprotection under physiological conditions. Contribution to ocular mucosal innate responses is dependent on the aetiology of immunological challenge.Radhika SusarlaLei LiuElizabeth A WalkerIwona J BujalskaJawaher AlsalemGeraint P WilliamsSreekanth SreekantamAngela E TaylorMohammad TallouziH Susan SouthworthPhilip I MurrayGraham R WallaceSaaeha RauzPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e94913 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Radhika Susarla Lei Liu Elizabeth A Walker Iwona J Bujalska Jawaher Alsalem Geraint P Williams Sreekanth Sreekantam Angela E Taylor Mohammad Tallouzi H Susan Southworth Philip I Murray Graham R Wallace Saaeha Rauz Cortisol biosynthesis in the human ocular surface innate immune response.
description	Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in OcS defense, remains unresolved. We found that primary human corneal epithelial cells (PHCEC), fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was independent of Toll-like receptor (TLR) activation. While PolyI∶C induced maximal cytokine and chemokine production from both PHCEC (IFNγ, CCL2, CCL3, and (CCL4), IL6, CXCL10, CCL5, TNFα) and PHKF (CCL2, IL-6, CXCL10, CCL5), only PHKF cytokines were inhibited by GCs. Both Poly I∶C and LPS challenged-corneal cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1 11β-HSD1 activity (30 and 40% respectively). These data were supported by clinical studies demonstrating reduced human tear film cortisol∶cortisone ratios (a biomarker of local 11β-HSD1 activity) in pseudomonas keratitis (1∶2.9) versus healthy controls (1∶1.3; p<0.05). This contrasted with putative TLR3-mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where an increase in cortisol∶cortisone ratio was observed (113.8∶1; p<0.05). In summary, cortisol biosynthesis in human corneal cells is independent of TLR activation and is likely to afford immunoprotection under physiological conditions. Contribution to ocular mucosal innate responses is dependent on the aetiology of immunological challenge.
format	article
author	Radhika Susarla Lei Liu Elizabeth A Walker Iwona J Bujalska Jawaher Alsalem Geraint P Williams Sreekanth Sreekantam Angela E Taylor Mohammad Tallouzi H Susan Southworth Philip I Murray Graham R Wallace Saaeha Rauz
author_facet	Radhika Susarla Lei Liu Elizabeth A Walker Iwona J Bujalska Jawaher Alsalem Geraint P Williams Sreekanth Sreekantam Angela E Taylor Mohammad Tallouzi H Susan Southworth Philip I Murray Graham R Wallace Saaeha Rauz
author_sort	Radhika Susarla
title	Cortisol biosynthesis in the human ocular surface innate immune response.
title_short	Cortisol biosynthesis in the human ocular surface innate immune response.
title_full	Cortisol biosynthesis in the human ocular surface innate immune response.
title_fullStr	Cortisol biosynthesis in the human ocular surface innate immune response.
title_full_unstemmed	Cortisol biosynthesis in the human ocular surface innate immune response.
title_sort	cortisol biosynthesis in the human ocular surface innate immune response.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/d2bd508f07b346feb6cb34bfdf15e08a
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Cortisol biosynthesis in the human ocular surface innate immune response.

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