Interleukin-1beta mediates human airway epithelial cell migration via NF-kappaB.
Migration of airway epithelial cells (AEC) is a necessary component of airway mucosal repair after injury. The cytokine IL-1beta, present in airway inflammation, has protean effects on constituent cells within the mucosa, but its effects on epithelial repair are not known. We examined migration in differentiated primary human AEC grown in air-liquid interface culture for up to 3 wk and in the 16HBE14o(-) cell line. Wounds were created by mechanical abrasion and followed to closure using digital microscopy. Concurrent treatment with IL-1beta (<or=10 ng/ml) significantly accelerated migration in primary differentiated cells and in the 16HBE14o(-) cell line but did not accelerate migration in primary differentiated AEC collected from asthmatic donors. IL-1beta treatment did not augment phosphorylation of stress-activated protein kinases normally activated by mechanical injury, such as heat shock protein 27, ERK1/2, and JNK, and did not elicit phosphorylation of signal transducer and activator of transcription-3. However, introduction of a silencing RNA to block expression of the p65 component of NF-kappaB blocked IL-1beta-accelerated migration substantially. Our data demonstrate that IL-1beta accelerates migration of normal, but not asthmatic, differentiated AEC by a mechanism that requires activation of the NF-kappaB signaling complex and suggests a trophic role for this cytokine in airway epithelial repair after injury.
White
Steven R
SR
Univ. of Chicago, Section of Pulmonary and Critical Care Medicine, 5841 S. Maryland Ave., MC 6076, Chicago, IL 60637, USA. swhite@medicine.bsd.uchicago.edu
Fischer
Bernard M
BM
Marroquin
Bertha A
BA
Stern
Randi
R
D001249:Asthma / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects* / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018832:Molecular Chaperones; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism*
D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D018832:Molecular Chaperones; C498143:RELA protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051996:Transcription Factor RelA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4