Interleukin-10 Regulates Transforming Growth Factor-β Signaling in Cultured Human Bronchial Epithelial Cells

Abstract

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)-β, 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. Objectives: 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-β-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.

ERK1/2 Signaling Pathway Modulates the Airway Smooth Muscle Cell Phenotype in the Rat Model of Chronic Asthma

“…This view, however, is rapidly changing because of the discovery that airway smooth muscles can undergo hyperplasia and/or hypertrophy, which can lead to structural changes in the airway obstruction and increased nonspecific airway hyperreactivity in chronic severe asthma [25, 26]. In addition, more recent studies have concentrated on the phenotypic transition of ASMCs from the contractile type to a more synthetic type in chronic asthmatics that enable the cells to gain secretory ability and become a rich source of many cytokines, chemokines and inflammatory mediators, which may modulate airway inflammation and processes of airway remodeling in asthma [27,28,29,30,31]. …”

Selective Depletion of Alveolar Macrophages in Polymicrobial Sepsis Increases Lung Injury, Bacterial Load and Mortality but Does Not Affect Cytokine Release

“…AM directly contribute to surfactant metabolism and are thought to be crucially involved in the generation of acute as well as chronic allergic reactions of the respiratory tract. In this context, the biology of AM has been extensively studied and both protective as well as detrimental functions of AM could be elucidated in different models of asthma and allergic airway diseases [7,8,9,10,11,12,13,14,15]. Previous studies have suggested that AM may also play a role in the development of secondary pulmonary disorders like acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) [16, 17].…”

Interleukin-10 deficiency aggravates kidney inflammation and fibrosis in the unilateral ureteral obstruction mouse model

“…[10][11][12] The underlying mechanism of antifibrotic effects of IL-10 remains unclear, but it has been suggested that IL-10 can suppress extracellular matrix synthesis and inhibit key inflammatory pathways such as NF-kB. [13][14][15] In the context of kidney, IL-10 has been reported to effectively suppress the progression of acute and chronic renal damage in vivo. [16][17][18][19][20][21][22] However, the role of IL-10 in renal tubulointerstitial fibrosis has not been studied.…”