Lipoxin A4Counter-regulates Histamine-stimulated Glycoconjugate Secretion in Conjunctival Goblet Cells.
Conjunctival goblet cells synthesize and secrete mucins which play an important role in protecting the ocular surface. Pro-resolution mediators, such as lipoxin A4(LXA4), are produced during inflammation returning the tissue to homeostasis and are also produced in non-inflamed tissues. The purpose of this study was to determine the actions of LXA4on cultured human conjunctival goblet cell mucin secretion and increase in intracellular [Ca2+] ([Ca2+]i) and on histamine-stimulated responses. LXA4increased mucin secretion and [Ca2+]i, and activated ERK1/2 in human goblet cells. Addition of LXA4before resolvin D1 (RvD1) decreased RvD1 responses though RvD1 did not block LXA4responses. LXA4inhibited histamine-stimulated increases in mucin secretion, [Ca2+]i, and ERK1/2 activation through activation of β-adrenergic receptor kinase 1. We conclude that conjunctival goblet cells respond to LXA4through the ALX/FPR2 receptor to maintain homeostasis of the ocular surface and regulate histamine responses and could provide a new therapeutic approach for allergic conjunctivitis and dry eye diseases.
Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA.
Robin R
RR
Hodges
Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA.
Dayu
D
Li
Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA.
Marie A
MA
Shatos
Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, 02115, USA.
Charles N
CN
Serhan
Schepens Eye Research Institute/Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA, 02114, USA.|Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Department of Anesthesiology, Perioperative, and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, 02115, USA.
Darlene A
DA
Dartt
D000818:Animals; D003228:Conjunctiva / Q000378:metabolism*; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D020397:Goblet Cells / Q000166:cytology / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D044045:Lipoxins / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009077:Mucins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005136:Eye Proteins; D044045:Lipoxins; D009077:Mucins; C040527:lipoxin A4; D006632:Histamine