Interleukin-10 regulates transforming growth factor-beta signaling in cultured human bronchial epithelial cells.
BACKGROUND
The basic pathological features of bronchial asthma can be explained on the basis of chronic airway inflammation, involving inflammatory cells such as T cells (particularly type 2 helper T, Th2, cells) and mast cells, and airway remodeling. Many aspects of airway remodeling remain unclear at the molecular level. Recent attention has focused on the role of transforming growth factor (TGF)-beta, a fibrogenic cytokine, in airway remodeling. Currently available evidence suggests that airway remodeling is caused by an imbalance in regulatory mechanisms mediated by Smads, a family of signal-transducing molecules.


OBJECTIVE
We studied the effects of the Th2 cytokines interleukin (IL)-5 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the regulatory cytokine IL-10 on the expression of inhibitory Smad7 protein in bronchial epithelial cells.


METHODS
Real-time reverse-transcriptase polymerase chain reaction was employed.


RESULTS
Stimulation with IL-10 upregulated the expression of Smad7 compared with control. Neither IL-5 nor GM-CSF induced Smad7 expression. Smad7 expression was upregulated by IL-10 plus either IL-5 or GM-CSF. IL-10 inhibited the expression of TGF-beta-inducible early gene, which is known to downregulate Smad7 expression.


CONCLUSIONS
Our results suggest that IL-10 acts as a regulatory cytokine in the inhibition of airway inflammation.
Fueki
Naoto
N
Department of Pulmonary Medicine and Clinical Immunology, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
Sagara
Hironori
H
Akimoto
Kazumi
K
Ota
Mayumi
M
Okada
Takenori
T
Sugiyama
Kumiya
K
Fueki
Makoto
M
Makino
Sohei
S
Fukuda
Takeshi
T
D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D051765:Early Growth Response Transcription Factors / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D015848:Interleukin-5 / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics*; D053701:Receptors, Interleukin-10 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D051906:Smad7 Protein / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers
D051765:Early Growth Response Transcription Factors; D015848:Interleukin-5; C098111:KLF10 protein, human; D051741:Kruppel-Like Transcription Factors; D053701:Receptors, Interleukin-10; C497806:SMAD7 protein, human; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D012313:RNA