title: Cis-urocanic acid inhibits SAPK/JNK signaling pathway in UV-B exposed human corneal epithelial cells in vitro.
abstract: OBJECTIVE
  The cornea is sensitive to ultraviolet B (UV-B) radiation-induced oxidative stress and inflammation. Its clinical manifestations are photokeratitis and climatic droplet keratopathy. Urocanic acid (UCA) is a major endogenous UV-absorbing chromophore in the epidermis and it is also an efficacious immunosuppressant. We have previously shown that cis-UCA can suppress UV-B-induced interleukin-6 and -8 secretion and cytotoxicity in human corneal epithelium (HCE) cells. In the current study, we further wanted to investigate the effects of cis-UCA on UV-B-induced inflammatory and apoptotic responses in HCE-2 cells, focusing on the nuclear factor kappa B (NF-κB) and AP-1 (subunits c-Fos and c-Jun) signaling pathways.
  
  
  METHODS
  After exposing HCE-2 cells to UV-B and cis-UCA, DNA binding of c-Fos, c-Jun and NF-κB was measured with ELISA. In addition, the endogenous levels of phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase (phospho-SAPK/JNK) and phospho-c-Jun were determined. The proliferative capacity of HCE-2 cells was also quantified, and the cytotoxicity of the cis-UCA and UV-B treatments was monitored by measuring the release of lactate dehydrogenase enzyme in the culture medium.
  
  
  RESULTS
  UV-B irradiation induced the binding of transcription factors c-Jun, c-Fos, and NF-κB to DNA. Cis-UCA inhibited the binding of c-Jun and c-Fos but not that of NF-κB. Moreover, UV-B increased the levels of phospho-c-Jun and phospho-JNK, and the expression of both was attenuated by cis-UCA. Cis-UCA also alleviated the UV-B-induced apoptosis and proliferative decline in human corneal cells.
  
  
  CONCLUSIONS
  The results from this study suggest that cis-UCA suppresses JNK signaling pathway, which provides potential for treating UV-B-induced inflammatory defects in human corneal cells.
authors.affiliation: Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hanna-Mari
authors.initials: HM
authors.lastname: Jauhonen
authors.forename: Anu
authors.initials: A
authors.lastname: Kauppinen
authors.forename: Tuomas
authors.initials: T
authors.lastname: Paimela
authors.forename: Jarmo K
authors.initials: JK
authors.lastname: Laihia
authors.forename: Lasse
authors.initials: L
authors.lastname: Leino
authors.forename: Antero
authors.initials: A
authors.lastname: Salminen
authors.forename: Kai
authors.initials: K
authors.lastname: Kaarniranta
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D020935:MAP Kinase Signaling System / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects; D014560:Urocanic Acid / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D007770:L-Lactate Dehydrogenase; D048031:JNK Mitogen-Activated Protein Kinases; D014560:Urocanic Acid