Inhibitory Effects of Tranilast on Cytokine, Chemokine, Adhesion Molecule, and Matrix Metalloproteinase Expression in Human Corneal Fibroblasts Exposed to Poly(I:C).
Purpose/Aim: Viral infection of the cornea can result in inflammation and scarring and eventually cause blindness. Polyinosinic-polycytidylic acid [poly(I:C)], an analog of viral double-stranded RNA, induces the synthesis of various cytokines, chemokines, adhesion molecules, and matrix metalloproteinases (MMPs) in corneal fibroblasts. The effects of tranilast on the expression of these molecules in human corneal fibroblasts were examined.



Human corneal fibroblasts were cultured with or without poly(I:C) or tranilast. The release of the proinflammatory cytokine interleukin (IL)-6 and of the chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) was measured with enzyme-linked immunosorbent assays. The expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), MMP-1, and MMP-3 was evaluated by immunoblot or immunofluorescence analysis. The phosphorylation of mitogen-activated protein kinases (MAPKs), c-Jun (a component of the transcription factor AP-1), and IκB-α (an endogenous inhibitor of the transcription factor NF-κB) was examined by immunoblot analysis.



Tranilast inhibited in a concentration- and time-dependent manner the production of IL-6, IL-8, MCP-1, ICAM-1, VCAM-1, MMP-1, and MMP-3 by corneal fibroblasts exposed to poly(I:C). It also inhibited the poly(I:C)-induced phosphorylation of c-Jun and the MAPK JNK without affecting that of IκB-α or the MAPKs ERK and p38.



Tranilast inhibited proinflammatory cytokine, chemokine, adhesion molecule, and MMP expression in human corneal fibroblasts exposed to poly(I:C), with these effects likely being mediated by attenuation of JNK-AP-1 signaling. Tranilast might therefore be expected to limit immune cell infiltration and stromal degradation associated with viral infection of the cornea.
a Department of Pathology , First Hospital of Jilin University , Jilin , PR , China.
Ye
Y
Liu
b Department of Biochemistry , College of Basic Medicine, Jilin University , Jilin , PR China.
Mujie
M
Kan
c Department of Ophthalmology , First Hospital of Jilin University , Jilin , PR China.
Aipeng
A
Li
c Department of Ophthalmology , First Hospital of Jilin University , Jilin , PR China.
Lulu
L
Hou
c Department of Ophthalmology , First Hospital of Jilin University , Jilin , PR China.
Hui
H
Jia
d Key Laboratory of Pathology, Ministry of Education , Jilin University , Jilin , PR China.
Ying
Y
Xin
c Department of Ophthalmology , First Hospital of Jilin University , Jilin , PR China.
Yang
Y
Liu
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis* / Q000187:drug effects; D003315:Cornea / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000187:drug effects; D011070:Poly I-C / Q000494:pharmacology; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018925:Chemokines; D016207:Cytokines; D062367:ortho-Aminobenzoates; D020782:Matrix Metalloproteinases; C012293:tranilast; D011070:Poly I-C
Corneal fibroblast; inflammation; matrix metalloproteinase; polyinosinic–polycytidylic acid; viral infection