Signalling pathways involved in ribonuclease-7 expression.
Antimicrobial peptides are host defence molecules that play a potential role in preventing infection at the epithelial surfaces. Ribonuclease (RNase)-7 has been shown to possess a broad spectrum of microbicidal activity against various pathogens. Here, we demonstrate that RNase-7 protein is localised to the superficial layers of ocular surface cells and increased in response to interleukin (IL)-1β, suggesting an active role during inflammation related to ocular surface infection. Signal transduction pathways involved in RNase-7 expression are unknown. Involvement of transforming growth factor β-activated kinase-1 (TAK-1) activated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway molecules [c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38] were studied because of their importance in infection and inflammation. Blocking the MAPKs resulted in inhibition of RNase-7 expression in response to IL-1β. However, RNase-7 induction by IL-1β was not affected by inhibiting the NF-κB signalling pathway. In conclusion, our results indicate that RNase-7 expression is specifically mediated via MAPKs but not NF-κB signalling pathways.
Mohammed
Imran
I
Larry A Donoso Laboratory for Eye Research, Division of Ophthalmology and Visual Sciences, University Hospital, Nottingham NG7 2UH, UK.
Yeung
Aaron
A
Abedin
Asiya
A
Hopkinson
Andrew
A
Dua
Harminder S
HS
D015153:Blotting, Western; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D015971:Gene Expression Regulation, Enzymologic; D020868:Gene Silencing; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
D053583:Interleukin-1beta; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D020928:Mitogen-Activated Protein Kinases; D012260:Ribonucleases; C470000:Ribonuclease 7