Airway diseases such as chronic rhinosinusitis, asthma, and chronic obstructive pulmonary disorder are characterized by inflammation and remodeling. Among inflammatory and extracellular matrix regulatory cytokines, transforming growth factor-beta (TGF-b) stands central, as it possesses both important immunomodulatory and fibrogenic activities, and should be considered a key for understanding inflammation and remodeling processes. This review will briefly summarize the recent findings on the role of TGF-b1, from the view points of inflammation and remodeling, and discuss the role of TGF-b in the upper and lower airway diseases. This may reveal new perspectives in the understanding of airway inflammation and remodeling processes and may open innovative treatment strategies for the regulation of TGF-b1.

Transforming growth factor-beta 1 (TGF-b1) has been reported being involved in the remodeling and immunosuppression processes of inflammatory airway diseases; understanding the regulation of TGF-b1 is therefore a key to unravel the pathomechanisms of these diseases. This review briefly summarizes the current knowledge on the influencing factors for driving TGF-b1 and its regulatory pathways in inflammatory airway diseases and discusses possible therapeutic approaches to TGF-b1 control. The factors include smoking and oxidative stress, prostaglandins (PGs), leukotrienes (LTs), bradykinin (BK), and microRNAs (miRs). Based on the summary, new innovative treatment strategies may be developed for inflammatory airway diseases with an impaired expression of TGF-b1.The transforming growth factor-beta (TGF-b) superfamily is critically involved in embryonic development, organogenesis, and tissue homeostasis. It acts as multifunctional regulators of cell growth and differentiation and consists of more than 40 members, mainly including TGF-bs, bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs), activins, and inhibins. Between these superfamily members, there is a complex network of regulatory mechanisms (1, 2).Possessing immunomodulatory and fibrogenic characteristics, TGF-b1 is a pleiotropic and multifunctional cytokine secreted from various types of cells, such as endothelial, epithelial and smooth muscle cells, as well as fibroblasts and most immune system cells.Transforming growth factor-beta 1 regulation is unique because it is targeted to the extracellular matrix as a biologically inactive complex, which consists of a mature 25-kDa polypeptide dimer (TGF-b), a latency-associated protein (LAP), and a latent TGF-b-binding protein (LTBP). Active TGF-b is released from the latent complex that was activated via cleavage by proteases and other molecules. The activated TGF-b then becomes a ligand for TGF-b type I and II receptors, leading to receptor Smad (R-Smad) phosphorylation, which subsequently binds to the common-partner Smad (co-Smad), and becoming Smad complexes. The Smad complexes translocate into the nucleus and combine with several transcription factors, thereby becoming a transcriptional active complex that activates target genes transcription. In Abbreviations AHR, airway hyper-responsiveness; BAMBI, BMP and activin membrane-bound inhibitor; BK, bradykinin; BMP, bone morphogenetic protein; CCL2/MCP-1, chemokine (CC motif) ligand 2/monocyte chemotactic protein-1; COPD, chronic obstructive pulmonary disease; CRS, chronic rhinosinusitis; CysLT, cysteinyl leukotriene; FoxP3, forkhead box P3; LAP, latency-associated protein; LTBP, latent TGF-b-binding protein; miR, microRNA; PG, prostaglandin; RORc, RAR-related orphan receptor C; TGF-b1, transforming growth factor-beta 1.Allergy 69 (2014) 699-707

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