Transient receptor potential vanilloid 1 activation induces inflammatory cytokine release in corneal epithelium through MAPK signaling.
In certain epithelial tissues, activation of transient receptor potential (TRP) vanilloid subtype 1 (TRPV1) by noxious stimuli induces pro-inflammatory cytokine release, which helps to mitigate the challenge. While the corneal epithelium elicits such responses to a variety of challenges, it remains unknown whether TRPV1 mediates pro-inflammatory cytokine secretion. Accordingly, we probed for TRPV1 expression and function in human (HCEC) and rabbit corneal epithelial cell (RCEC) lines, in their primary counterparts, and in human and mouse corneal epithelium in situ. Cell membrane and perinuclear TRPV1 expression was detected in all preparations and its identity verified by Western blot analysis. Capsaicin (CAP) (1-10 microM) increased nonselective cation channel whole cell currents (2.5-fold +/- 0.5-fold between -60 and 130 mV), resulting in calcium transients that were fully blocked by the TRPV1 antagonists capsazepine (CPZ) and ruthenium red, or removal of extracellular calcium. Another signaling event involved transient activation of global mitogen-activated protein kinase (MAPK) superfamily, which was followed by up to 3.3- and 9-fold increases in interleukins (IL)-6 and -8 release, respectively. Such increases in inflammatory mediators' release were suppressed by exposure to CPZ or MAPK inhibitors, or removal of Ca2+. Taken together, TRPV1 receptors may play a role in mediating corneal epithelial inflammatory mediator secretion and subsequent hyperalgesia.
Zhang
Fan
F
Biological Sciences, the State University of New York, College of Optometry, New York, New York 10036, USA.
Yang
Hua
H
Wang
Zheng
Z
Mergler
Stefan
S
Liu
Hongshan
H
Kawakita
Tetsuya
T
Tachado
Souvenir D
SD
Pan
Zan
Z
Capó-Aponte
José E
JE
Pleyer
Uwe
U
Koziel
Henry
H
Kao
Winston W Y
WW
Reinach
Peter S
PS
D000650:Amnion / Q000166:cytology; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D018929:Cell Culture Techniques; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D003315:Cornea / Q000166:cytology; D004594:Electrophysiology; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000378:metabolism*
D000952:Antigens, Polyomavirus Transforming; D015850:Interleukin-6; D016209:Interleukin-8; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; C493921:TRPV1 protein, mouse; D020928:Mitogen-Activated Protein Kinases; D002118:Calcium