Human TGF-beta1 ELISA

Features

• RUO
• calibration range 31-2000 pg/ml
• limit of detection 8.6 pg/ml
• intra-assay CV = 3.2%
• inter-assay CV = 4.9%

Research topic

Cytokines and chemokines and related molecules

Summary

Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that exhibits a broad spectrum of biological and regulatory effects on the cellular and organism level. It plays a critical role in cellular growth, development, differentiation, proliferation, extracellular matrix (ECM) synthesis and degradation, control of mesenchymal-epithelial interactions during embryogenesis, immune modulation, apoptosis, cell cycle progression, angiogenesis, adhesion and migration and leukocyte chemotaxis. It has both tumor suppressive and tumor promoting activities and is highly regulated at all levels (e.g.: mRNA turnover, latent protein activation or post-translational modifications). TGF-β is the first recognized protein of at least 40 of the TGF-β superfamily of structurally related cytokines. Three isoforms (TGF-β 1-3) have been described in mammals. (Each isoform is encoded by a unique gene on different chromosomes. All bind to the same receptors.) They are synthesized by most cell types and tissues. Cells of the immune system mainly express TGF-β 1. The initially sequestered, inactive LTGF-β (latent TGF-β) requires activation (cleavage and dissociation of its LAP (latency associated peptide) region) before it can exert biological activity. LTGF-β can also be bound to LTB (latent TGF-β binding protein) to form a large latent complex (LLC). TGF-β forms homodimers, and its subunits of 12.5 kDa each are bound via disulphide bridges. TGF-β signal transduction is mediated via the TGF-β receptors Type II and I, phosphorylation and conformational changes, followed by different pathways: SMAD ( - pathway: TGF-β recruitment finally leads to phosphorylation of receptor-regulated SMADs (R-SMADs = SMAD 2, 3) and binding of common SMAD (coSMAD = SMAD 4). The R-SMAD/ coSMAD complex enters the nucleus and interacts with a number of transcription factors, coactivators and corepressors. TGF-β induces MAPK- and MAP/ERK kinase dependent signal transduction (JNK/MAPK-, JNK/SPAK-, p38-, ERK1/2 - pathway) and the NF-κB – pathway. TGF-β mediates cell cycle growth arrest via the phosphoinositide 3-kinase/Akt pathway. TGF-β signaling is highly regulated e.g. via interaction with inhibitory SMADs (I-SMADs = SMAD 6, 7) or binding of the E3-ubiquitin ligases Smurf1 and Smurf2 or/and coreceptors. TGF-β1 is the key mediator in the pathophysiology of tissue repair and human fibrogenesis: balance between production and degradation of type I collagen, and fibrosis and scarring in organ and tissue. TGF-β1 exhibits important immunoregulatory features of partially adverse character: TGF-β1 inhibits B and T cell proliferation, differentiation and antibody production as well as maturation and activation of macrophages. It inhibits activity of NK cells and lymphokine activated killer cells and blocks production of cytokines. TGF-β1 promotes Treg cell differentiation resulting in IL-10/TGF-β1 production and Th1 cell and Th2 cell suppression. TGF-β1 was recently shown to promote Th17 development in the presence of IL-6 or IL-21 in mice and probably plays a role in human Th17 development together with IL-1β, IL-21 and IL-23. In this context TGF-β1 is involved in induction and mediation of proinflammatory and allergic responses.