Further Characterization of Activin A-induced IgA Response in Murine B Lymphocytes

Lee, Hwa-Joung; Kim, Pyeung-Hyeun

doi:10.4110/in.2009.9.4.133

Cited by 9 publications

(11 citation statements)

References 20 publications

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“…The effects of activin-A neutralization during allergic responses were observed even in the presence of endogenous TGF-b 1 , suggesting that these two cytokines, as also shown in other studies, should not be considered as redundant during inflammatory processes [24,25,27,28,42,44,45,53,60,62,63,65]. In support, activin-A and TGF-b 1 induce different Treg subsets, indicating that, at least in the Th2 setting, these factors operate through distinct suppressive mechanisms.…”

Section: Activin-a In the Regulation Of Experimental Asthmasupporting

confidence: 69%

“…In addition, r-activin-A inhibits IL-6-driven mouse B cell proliferation and monocyte phagocytosis in vitro [27,52]. Activin-A increases IgA production from mouse mesenteric lymph node cells, pointing to a role for this cytokine in the maintenance of intestinal immune homeostasis [53]. In humans, in vitro studies have demonstrated that treatment of peripheral blood DCs with follistatin considerably enhances CD40Linduced pro-inflammatory cytokine and chemokine release, as well as, DC-driven CD8 1 T cell proliferation and IFN-g production [24].…”

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

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Activin‐A: a novel critical regulator of allergic asthma

Kariyawasam

Semitekolou

Robinson

et al. 2011

Clin Experimental Allergy

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Activin-A is a pleiotropic cytokine that belongs to the TGF-β superfamily and plays an important role in fundamental biological processes, such as development and tissue repair. Growing evidence proposes a crucial role for activin-A in immune-mediated responses and associated diseases, with both enhancing and suppressive effects depending on the cell type, the cytokine micromilieu and the context of the response. Several recent studies have demonstrated a striking increase in activin-A expression in experimental models of asthma, as well as, in the asthmatic airway in humans. Importantly, a strong immunoregulatory role for activin-A in allergic airway disease, with suppression of T helper (Th) type 2 cell-driven allergic responses and protection against the development of cardinal features of the asthmatic phenotype was revealed by in vivo functional studies. Activin-A-mediated immunosuppression is associated with induction of functional allergen-specific regulatory T cells. In human asthma, although activin-A levels are increased in the airway epithelium and submucosal cells, the expression of its signalling components is markedly decreased, pointing to decreased regulation. Nevertheless, a rapid activation of the activin-A signalling pathway is observed in the airway of individuals with asthma following inhalational allergen challenge, suggestive of an inherent protective mechanism to control disease. In support, in vitro studies using human airway epithelial cells have demonstrated that endogenous activin-A suppresses the release of inflammatory mediators, while it induces epithelial repair. Collectively, compelling evidence suggests that activin-A orchestrates the regulation of key events involved in the pathogenesis of allergic asthma. The critical role of activin-A in allergic airway responses places this cytokine as an exciting new therapeutic target for asthma.

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Section: Activin-a In the Regulation Of Experimental Asthmasupporting

confidence: 69%

Section: Anti-inflammatory Effectsmentioning

confidence: 99%

Activin‐A: a novel critical regulator of allergic asthma

Kariyawasam

Semitekolou

Robinson

et al. 2011

Clin Experimental Allergy

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“…These data demonstrate that ActA is not an OCL survival factor, but when administered in combination with RANKL, ActA significantly inhibits RANKL-induced OCL maturation, survival and fusion. Given that ActA has been shown to regulate the lifespan of other hematopoietic cell types (Lee and Kim, 2009;Valderrama-Carvajal et al, 2002), the specific effects of ActA on the survival of mature OCL and their precursors was also examined.…”

Section: Discussionmentioning

confidence: 99%

Activin A inhibits RANKL-mediated osteoclast formation, movement and function in murine bone marrow macrophage cultures

Fowler

Kamalakar

Akel

et al. 2015

Journal of Cell Science

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BSTRACTThe process of osteoclastic bone resorption is complex and regulated at multiple levels. The role of osteoclast (OCL) fusion and motility in bone resorption are unclear, with the movement of OCL on bone largely unexplored. RANKL (also known as TNFSF11) is a potent stimulator of murine osteoclastogenesis, and activin A (ActA) enhances that stimulation in whole bone marrow. ActA treatment does not induce osteoclastogenesis in stroma-free murine bone marrow macrophage cultures (BMM), but rather inhibits RANKL-induced osteoclastogenesis. We hypothesized that ActA and RANKL differentially regulate osteoclastogenesis by modulating OCL precursors and mature OCL migration. Time-lapse video microscopy measured ActA and RANKL effects on BMM and OCL motility and function. ActA completely inhibited RANKLstimulated OCL motility, differentiation and bone resorption, through a mechanism mediated by ActA-dependent changes in SMAD2, AKT1 and inhibitor of nuclear factor kB (IkB) signaling. The potent and dominant inhibitory effect of ActA was associated with decreased OCL lifespan because ActA significantly increased activated caspase-3 in mature OCL and OCL precursors.Collectively, these data demonstrate a dual action for ActA on murine OCLs.

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“…25 In addition, an alternative mechanism for the induction of activin A by human bone marrow monocytes is through the cognate interaction with activated T cells requiring the CD40-CD40L interaction and T-cell-derived cytokines such as GM-CSF and interferon-g (IFN-g). 29 Mo-DCs and peripheral CD1c + myeloid DCs CD40L and agonists for TLR4 (LPS), -3 (poly-I:C) and -7/8 (R848) m activin A 72 A m IL-10, TNF-a, IL-6 and IL-12p70, MCP-1, RANTES, IL-8 and IP-10 84,85 B9 and MPC-11 cell lines Activin A promotes apoptosis 82 Splenic B cells and CH12F3-2 B-cell lymphoma Activin A sensitizes resting B cells to produce IgG after LPS activation [86][87][88] Activin A m IgA production induced by LPS…”

Section: Monocytesmentioning

confidence: 99%

“…More specifically, activin A enhanced IgA expression induced by LPS, and this effect appeared to be mediated by the induction of GLT a (Ig germline a) and PST a (post-switch transcripts a) in B-lymphoma cells and normal mouse-spleen B cells (Figure 3b). 87,88 Thus, activin A released by activated B cells has been proposed to regulate the antibody isotype switching in the spleen, acting on resting B cells, which, once activated, show upregulation of IgG isotype antibodies and, in this way, participate in the fine tuning of humoral responses. So far, it is unknown whether the expression and signaling of activin A can be regulated directly by the B-cell receptor as a possible crosstalk between both pathways.…”

Section: Role Of Activins/inhibins On Adaptive Immune Cells B Cellsmentioning

confidence: 99%

When versatility matters: activins/inhibins as key regulators of immunity

Alemán-Muench

Soldevila

2011

Immunol Cell Biol

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Activins and inhibins are members of the transforming growth factor-b superfamily that have been considered crucial regulators of cell processes, such as differentiation, proliferation and apoptosis, in different cell types. Initial studies about the function of activin A in the immune system focused on the regulation of hematopoiesis in the bone marrow under homeostatic and inflammatory conditions. Recent data provide a more comprehensive understanding about the role of activins/inhibins in the immune system. Novel findings included in this review point out the important requirement of activin/inhibin signaling to maintain the balance between homeostatic and inflammatory signals that are required for the optimal development and function of immune cells. The purpose of this review is to highlight the versatile nature of activins/inhibins as key regulators of both the innate and adaptive immune responses. Keywords: activin; inhibin; inflammation; immune cells; immunity; tolerance Activins and inhibins are members of the transforming growth factor-b (TGF-b) superfamily that were initially described as regulators of reproductive processes in mammals, and were first named after their positive and negative effect in the release of follicle-stimulating hormone from the pituitary gland, respectively. 1 These dimeric ligands have been shown to modulate a variety of cellular functions such as apoptosis, proliferation, differentiation, cellular migration, among others. 2,3 Activin A (bA/bA) is the best-characterized ligand of this subfamily, although there are other bioactive forms, activin B (bB/bB) and activin AB (bA/bB), which differ in their potency and cellular function. 4 Activin A is a molecule with pleiotropic functions, which shares with TGF-b the SMAD2/3 canonical signaling pathway (reviewed by Shi and Massague 5 ) but uses distinct type II (ActRIIs) and type I (ALK2, ALK4 and ALK7) receptors. [6][7][8][9] The biological function of activins can be blocked by follistatin (FS), a glycoprotein that binds activin A with high affinity, functioning as a ligand trap. 10 On the other hand, inhibins are heterodimers formed by uncommon a-and b-subunits and exist in two isoforms, inhibin A (a/bA) and B (a/bB). Inhibins have been shown to antagonize activinmediated functions by a mechanism that involves binding to b-glycan (TGFbRIII) and formation of a ternary complex with ActRIIs. As a consequence, activin type I receptors (ALK4 and ALK2) are excluded from the receptor complex, leading to the inhibition of SMADmediated signaling. 3,[11][12][13][14] Despite the fact that inhibins have been classically considered as activin antagonists, there is evidence showing that they do not always antagonize activin-mediated functions in several cell types, suggesting the existence of an independent inhibinmediated signaling pathway. 3 Compelling evidence has shown that activins also regulate various non-reproductive processes, such as mesoderm induction, liver proliferation, skin morphogenesis, erythropoiesis, bone formation, neu...

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Further Characterization of Activin A-induced IgA Response in Murine B Lymphocytes

Cited by 9 publications

References 20 publications

Activin‐A: a novel critical regulator of allergic asthma

Activin‐A: a novel critical regulator of allergic asthma

Activin A inhibits RANKL-mediated osteoclast formation, movement and function in murine bone marrow macrophage cultures

When versatility matters: activins/inhibins as key regulators of immunity

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