Premium
Ultraviolet B radiation activates NF‐κB and induces iNOS expression in HR‐1 hairless mouse skin: Role of IκB kinase‐β
Author(s) -
Chang EunJin,
Kundu Joydeb Kumar,
Liu Lijia,
Shin JunWan,
Surh YoungJoon
Publication year - 2011
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20646
Subject(s) - hairless , kinase , iκb kinase , biology , p38 mitogen activated protein kinases , phosphorylation , microbiology and biotechnology , nfkb1 , mapk/erk pathway , iκbα , nf κb , nitric oxide synthase , cancer research , signal transduction , transcription factor , biochemistry , enzyme , gene
Exposure to ultraviolet B (UVB) radiation is known to cause inflammatory tissue damage and skin cancer. One of the molecular links between inflammation and cancer is the eukaryotic transcription factor nuclear factor‐kappaB (NF‐κB), which is known to regulate expression of various pro‐inflammatory genes including inducible nitric oxide synthase (iNOS). The present study was aimed at elucidating the molecular mechanisms underlying UVB‐induced NF‐κB activation and iNOS expression in hairless mouse skin. Irradiation of male HR‐1 hairless mouse skin with UVB (5 kJ/m 2 ) resulted in increased degradation of IκBα, nuclear translocation of p65 and p50, and the DNA binding of NF‐κB. Exposure to UVB radiation induced the phosphorylation and the catalytic activity of an upstream kinase IκB kinase‐β (IKKβ). Pharmacological inhibition of IKKβ attenuated UVB‐induced NF‐κB activation in mouse skin. Irradiation of mouse skin with UVB also increased phosphorylation of extracellular signal‐regulated kinase (ERK) and p38 mitogen‐activated protein (MAP) kinase. Pretreatment with SC‐514, a specific inhibitor of IKKβ, attenuated UVB‐induced phosphorylation of ERK and p38 MAP kinase. A kinetic study showed that UVB significantly increased the expression of iNOS in mouse skin at 6 h postirradiation, which was abrogated by pretreatment with SC‐514. In conclusion, the upstream kinase IKKβ is involved in UVB‐induced activation of MAP kinases and NF‐κB, and expression of iNOS in mouse skin. © 2011 Wiley‐Liss, Inc.