VCAM-1 Activates Phosphatidylinositol 3-Kinase and Induces p120<i>Cbl</i>Phosphorylation in Human Airway Smooth Muscle Cells

Lazaar, Aili L.; Krymskaya, Vera P.; Das, Susan K. P.

doi:10.4049/jimmunol.166.1.155

Cited by 36 publications

(28 citation statements)

References 53 publications

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“…Human polyclonally activated T cells have been shown to adhere to ASM cells through integrins and CD44 and to induce myocyte DNA synthesis in vitro (8). In cultured ASM cells, the engagement of adhesion and immune receptors such as CD40, CD44, and VCAM-1 leads to signaling events that may be involved in proliferative responses including calcium mobilization (22), activation of MAPK and PI3K, and expression of cyclin D1 (23). In inflammatory bowel disease, where smooth muscle hyperplasia occurs in the muscularis mucosae, peripheral blood mononuclear cells interact with cultured muscularis mucosae myocytes through CD44 and VCAM-1 (24).…”

Section: Discussionmentioning

confidence: 99%

Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma

Ramos-Barbón¹,

Presley²,

Hamid³

et al. 2005

J. Clin. Invest.

111

122

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Section: Discussionmentioning

confidence: 99%

Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma

Ramos-Barbón¹,

Presley²,

Hamid³

et al. 2005

J. Clin. Invest.

111

122

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“…Immunoblot analyses of cyclin D1, p27 Kip1 , IFI 16, cyclin E, and cdk2 (both phosphorylated and nonphosphorylated forms) using whole cell lysates were performed as described previously (1,2,21). E2F-1 and Rb immunoblot analysis was performed using total nuclear protein extracts and HeLa cell lysates as positive controls (Santa Cruz Biotechnology, Santa Cruz, CA).…”

Section: Sds-page and Western Blot Analysismentioning

confidence: 99%

“…Kip1 (1,21). To address whether the effects of IFN-␥ on human ASM are mediated by inhibition of cyclin D1 expression or p27…”

Section: Ifn-␥ Does Not Inhibit Egf-or Thrombin-induced Pi3k or P70s6mentioning

confidence: 99%

IFN-γ inhibits human airway smooth muscle cell proliferation by modulating the E2F-1/Rb pathway

Amrani

Tliba

Choubey

et al. 2003

American Journal of Physiology-Lung Cellular and Molecular Phys

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Elucidating the factors that inhibit the increase in airway smooth muscle (ASM) mass may be of therapeutic benefit in asthma. Here, we investigated whether interferon-γ (IFN-γ), a potent inducer of growth arrest in various cell types, regulates mitogen-induced ASM cell proliferation. IFN-γ (1–100 U/ml) was found to markedly decrease both DNA synthesis and ASM cell number induced by the mitogens epidermal growth factor (EGF) and thrombin. Interestingly, IFN-γ had no effect on mitogen-induced activation of three major mitogenic signaling pathways, phosphatidylinositol 3-kinase, p70S6k, or mitogen-activated protein kinases. Mitogen-induced expression of cell cycle regulator cyclin D1 was increased by IFN-γ, whereas no effect was observed on degradation of p27Kip1. Expression array analysis of 23 cell cycle-related genes showed that IFN-γ inhibited EGF-induced increases in E2F-1 expression, whereas induction of c- myc, cyclin D2, Egr-1, and mdm2 were unaffected. Induction of E2F-1 protein and Rb hyperphosphorylation after mitogen stimulation was also suppressed by IFN-γ. In addition, IFN-γ decreased activation of cdk2 and expression of cyclin E, upstream signaling molecules responsible for Rb hyperphosphorylation in the late G1 phase. IFN-γ also increased levels of IFI 16 protein, whose mouse homolog p202 has been associated with growth inhibition. Together, our data indicate that IFN-γ is an effective inhibitor of ASM cell proliferation by blocking transition from G1-to-S phase by acting at two different levels: modulation of cdk2/cyclin E activation and inhibition of E2F-1 gene expression.

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“…Cells were stimulated as indicated in the figures, and cell lysates were prepared as previously described (29). Fifteen micrograms of protein was separated by SDS-PAGE on an 8% gel, transferred to a polyvinylidene difluoride membrane, and immunoblotted as previously described (29).…”

Section: Immunoblottingmentioning

confidence: 99%

“…Fifteen micrograms of protein was separated by SDS-PAGE on an 8% gel, transferred to a polyvinylidene difluoride membrane, and immunoblotted as previously described (29).…”

Section: Immunoblottingmentioning

confidence: 99%

Mast Cell Chymase Modifies Cell-Matrix Interactions and Inhibits Mitogen-Induced Proliferation of Human Airway Smooth Muscle Cells

Lazaar

Plotnick

Kucich

et al. 2002

The Journal of Immunology

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The hallmarks of chronic, severe asthma include prominent airway inflammation and airway smooth muscle (ASM) hypertrophy and hyperplasia. One of the factors that contribute to the injury and repair process within the airway is activation of proteases and turnover of extracellular matrix components. Mast cells, which are present in increased numbers in the asthmatic airway, are a rich source of the neutral protease chymase, which can degrade several basement membrane components. Recent data suggest that proteases also play a critical role in regulating the expression of CD44, the primary receptor for the matrix glycosaminoglycan hyaluronan. In this study we investigated the effects of chymase treatment on human ASM cell function. We found that chymase degraded the smooth muscle cell pericellular matrix. This was accompanied by an increased release of fibronectin and soluble CD44, but not soluble ICAM-1 or soluble hyaluronan, into the conditioned medium. In addition, chymase inhibited T cell adhesion to ASM and dramatically reduced epidermal growth factor-induced smooth muscle cell proliferation. These data suggest that the local release of mast cell chymase may have profound effects on ASM cell function and airway remodeling.

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VCAM-1 Activates Phosphatidylinositol 3-Kinase and Induces p120CblPhosphorylation in Human Airway Smooth Muscle Cells

Cited by 36 publications

References 53 publications

Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma

Antigen-specific CD4+ T cells drive airway smooth muscle remodeling in experimental asthma

IFN-γ inhibits human airway smooth muscle cell proliferation by modulating the E2F-1/Rb pathway

Mast Cell Chymase Modifies Cell-Matrix Interactions and Inhibits Mitogen-Induced Proliferation of Human Airway Smooth Muscle Cells

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