TNF-.ALPHA. augments the expression of RhoA in the rat bronchus

Sakai, Hiroyasu; Otogoto, Shinobu; Chiba, Yoshihiko; Abe, Kazuho; Misawa, Miwa

doi:10.1540/jsmr.40.25

Cited by 27 publications

(25 citation statements)

References 32 publications

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“…4) after application of TNF-α. Consistent with our previous rat study (22), TNF-α caused an upregulation of RhoA in hBSMCs. A significant increase in the level of RhoA mRNA was observed when the cells were stimulated with 10 ng/mL of TNF-α for 6, 12, and 24 h (Fig.…”

Section: Nf-κb Activation By Tnf-α In Hbsmcssupporting

confidence: 93%

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Tumor Necrosis Factor–α (TNF-α) Induces Upregulation of RhoA via NF-κB Activation in Cultured Human Bronchial Smooth Muscle Cells

et al. 2009

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Abstract. RhoA plays an important role in Ca 2+ sensitization of bronchial smooth muscle in antigen-induced airway hyperresponsiveness (AHR). Tumor necrosis factor-α (TNF-α), a major proinflammatory cytokine, is capable of inducing AHR, but the mechanisms for this are still unknown. In the present study, the effect of TNF-α on RhoA protein expression was examined in cultured human bronchial smooth muscle cells (hBSMCs). To investigate the role of NF-κB in the TNF-α-induced upregulation of RhoA, the effects of an inhibitor of IκB kinase (IKK), BMS-345541, were also determined. Both immunoblot and immunocytochemical analyses revealed that incubation of the hBSMCs with TNF-α caused an activation of NF-κB (determined by a translocation of p65 proteins to nuclei): the peak response was observed when cells were incubated with 10 ng/mL of TNF-α for 30 min. An upregulation of RhoA protein was also observed at 12 -24 h after the incubation with TNF-α (10 ng/mL). Both the activation of NF-κB and upregulation of RhoA were concentration-dependently inhibited by the co-incubation with BMS-345541. These results suggest that TNF-α-induced upregulation of RhoA might be mediated by an activation of NF-κB in hBSMCs.

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Section: Nf-κb Activation By Tnf-α In Hbsmcssupporting

confidence: 93%

“…A marked upregulation of RhoA in BSMs has also been demonstrated in these animal models of allergic bronchial asthma (14,15). Although the detailed mechanism(s) of RhoA upregulation is not fully understood, TNF-α might be one of the causes of the phenomenon (8,22).…”

Section: Introductionmentioning

confidence: 91%

Tumor Necrosis Factor–α (TNF-α) Induces Upregulation of RhoA via NF-κB Activation in Cultured Human Bronchial Smooth Muscle Cells

et al. 2009

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“…Additionally, we showed that in cultured human ASM cells TNFα potentiated, also in a non-specific manner, calcium signals in response to different GPCR agonists (Amrani, 2006). Parallel studies further supported the potential role of TNFα-ASM interaction in AHR by showing that TNFα acts by inducing Rho-dependent calcium sensitization (Hunter et al, 2003;Hunter and Nixon, 2006;MacEwan, 2002;McFarlane et al, 2001;Parris et al, 1999;Sakai et al, 2004b). Together, these investigators demonstrate that TNFα promotes AHR by modulating ASM contractility, an effect that could result from an altered GPCR-associated calcium signaling.…”

Section: Introductionmentioning

confidence: 57%

Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness

et al. 2008

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We recently identified autocrine interferon (IFN)β as a novel mechanism mediating tumor necrosis factor (TNF)α-induced expression of inflammatory genes in airway smooth muscle (ASM) cells, including CD38, known to regulate calcium signaling. Here, we investigated the putative involvement of IFNβ in regulating TNFα-induced airway hyper-responsiveness (AHR), a defining feature of asthma. Using our pharmacodynamic model to assess ex vivo AHR isolated murine tracheal rings, we found that TNFα-induced enhanced contractile responses to carbachol and bradykinin was abrogated by neutralizing anti-IFNβ antibody or in tracheal rings deficient in CD38. In cultured human ASM cells, where CD38 has been involved in TNFα-induced enhanced calcium signals to carbachol and bradykinin, we found that neutralizing anti-IFNβ prevented TNFα enhancing action only on carbachol responses but not to that induced by bradykinin. In a well-characterized model of allergic asthma (mice sensitized and challenged with Aspergillus fumigatus (Af)), we found heightened expression of both IFNβ and CD38 in the airways. Furthermore, allergen-associated AHR to methacholine, assessed by lung resistance and dynamic compliance, was completely suppressed in CD38-deficient mice, despite the preservation of airway inflammation. These data provide the first evidence that ASM-derived IFNβ and CD38 may play a significant role in the development of TNFα-associated AHR.

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“…TNF-a can activate RhoA/Rho kinase (46), and that inhibition of Rho kinase decreases airway inflammation (47) as well as airway hyperresponsiveness (48,49). Accordingly, it is possible that NT activation of p75NTR can modulate TNF-a effects (and vice versa) on ASM sensitivity for force generation.…”

Section: Tnf-a Nts and The Airwaymentioning

confidence: 99%

Brain-Derived Neurotrophic Factor in TNF-α Modulation of Ca²⁺ in Human Airway Smooth Muscle

Prakash¹,

Thompson²,

Pabelick³

2009

Am J Respir Cell Mol Biol

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There is increasing recognition that neurotrophin (NT) signaling occurs in non-neuronal tissues, including airway smooth muscle (ASM). We recently demonstrated that NTs, such as brain-derived neurotrophic factor (BDNF), enhance intracellular Ca 21 ([Ca 21 ] i ) and force regulation in human ASM. Increased NT expression has been observed in airway diseases, such as asthma and allergy. In the present study, we tested the hypothesis that NTs contribute to inflammation-induced enhancement of ASM contractility. Using human ASM cells and real-time fluorescence [Ca 21 ] i imaging, we examined the contribution of the high-affinity tropomyosin-related kinase and low-affinity, pan-NT p75NTR receptors to [Ca 21 ] i regulation under control conditions and after exposure to the proinflammatory cytokine TNF-a (20 ng/ml). Exposure to TNF-a enhanced [Ca 21 ] i responses to agonist (acetylcholine, histamine). Exposure to 10 nM BDNF for even 30 minutes substantially and synergistically enhanced TNF-a effects on [Ca 21 ] i responses to agonist. Small interfering RNA suppression of tropomyosin-related kinase substantially blunted the effect of BDNF on [Ca 21 ] i responses to agonist (with greater effect on Ca 21 influx via store-operated Ca 21 entry compared with sarcoplasmic reticulum Ca 21 release) in both control and TNF-a-exposed cells. However, p75NTR suppression by small interfering RNA had no significant effect on [Ca 21 ] i responses in either cell group. These novel data demonstrate that NTs influence ASM contractility, and suggest a potential role for NTs in airway diseases.

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TNF-.ALPHA. augments the expression of RhoA in the rat bronchus

Cited by 27 publications

References 32 publications

Tumor Necrosis Factor–α (TNF-α) Induces Upregulation of RhoA via NF-κB Activation in Cultured Human Bronchial Smooth Muscle Cells

Tumor Necrosis Factor–α (TNF-α) Induces Upregulation of RhoA via NF-κB Activation in Cultured Human Bronchial Smooth Muscle Cells

Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness

Brain-Derived Neurotrophic Factor in TNF-α Modulation of Ca²⁺ in Human Airway Smooth Muscle

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TNF-.ALPHA. augments the expression of RhoA in the rat bronchus

Cited by 27 publications

References 32 publications

Tumor Necrosis Factor–α (TNF-α) Induces Upregulation of RhoA via NF-κB Activation in Cultured Human Bronchial Smooth Muscle Cells

Tumor Necrosis Factor–α (TNF-α) Induces Upregulation of RhoA via NF-κB Activation in Cultured Human Bronchial Smooth Muscle Cells

Essential role of IFNβ and CD38 in TNFα-induced airway smooth muscle hyper-responsiveness

Brain-Derived Neurotrophic Factor in TNF-α Modulation of Ca2+ in Human Airway Smooth Muscle

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Brain-Derived Neurotrophic Factor in TNF-α Modulation of Ca²⁺ in Human Airway Smooth Muscle