T cell–derived microvesicles induce mast cell production of IL-24: Relevance to inflammatory skin diseases

Shefler, Irit; Pasmanik‐Chor, Metsada; Kidron, Dvora; Mekori, Yoseph A.; Hershko, Alon Y.

doi:10.1016/j.jaci.2013.04.035

Cited by 71 publications

(51 citation statements)

References 33 publications

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“…They supposed that this cytokine may have a role in the pathology of chronic pancreatitis cases. Whereas the exact mechanism responsible for IL-24/mda-7 expression is not described before, an involvement of MAPK pathway and STAT3 activation is under consideration (29,30).…”

Section: Discussionmentioning

confidence: 99%

The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells

et al. 2017

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Abstract. Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrosis. Interleukin (IL)-24/melanoma differentiation-associated gene-7 (mda-7) has attracted attention in the pathophysiology of some diseases, while its role in activation/suppression of human HSCs is still unclear. It is important to elucidate whether the expression levels of the IL-24/mda-7 protein and its receptors in HSC cells are changed following activation. LX-2 cells, a human hepatic stellate cell line were activated by a combination of leptin and serum starvation. The activation state was evaluated through measuring the mRNA expression of profibrotic molecules, collagen-I, TIMP metalloproteinase inhibitor-1 and transforming growth factor-β. The expression of IL-24/mda-7 was assessed in mRNA and protein levels by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA methods, respectively. Hence, the amount of IL-22R1 and IL-20R2 subunit expression was also compared in activated and normal LX-2 cells by RT-qPCR. The expression level of IL-24/mda-7 and its cognate receptors was detectable both in the normal and activated LX-2 cell line. Furthermore, in activated LX-2, a significant increase of IL24 expression either on IL-22R1 and IL-20R2 subunits was also noticeable in comparison to normal cells. The activation state of LX-2 cells caused significant changes of IL-24/mda-7 and its receptors expression. In addition, the elevation in IL-24/mda-7 during LX-2 cell activation, suggested that IL-24/mda-7 and its cognate receptors serve a possible role in the development of the fibrosis process. Therefore, IL-24/mda-7 and relevant signaling pathways may be employed as a target for fibrosis treatment.

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Section: Discussionmentioning

confidence: 99%

The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells

et al. 2017

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“…Flow cytometry Flow cytometry was performed as described previously [18]. Briefly, MVs obtained from CSF were fixed with 2 % PFA for about 15 min and then permeabilized with 0.1 % PBS-Tween for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

Jiang

et al. 2016

Purinergic Signalling

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Microglia are critical in the pathogenesis of neuropathic pain. In this study, we investigated the role of microvesicles (MVs) in neuropathic pain induced by spinal nerve ligation (SNL) in rats. First, we found that MVs shed from microglia were increased in the cerebrospinal fluid and dorsal horn of the spinal cord after SNL. Next, MVs significantly reduced paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). In addition, the P2X7-p38 pathway was related to the bleb of MVs after SNL. Interleukin (IL)-1β was found to be significantly upregulated in the package of MVs, and PWT and PWL increased following inhibition with shRNA-IL-1β. Finally, the amplitude and frequency of spontaneous excitatory postsynaptic currents increased following stimulation with MVs. Our results indicate that the P2X7-p38 pathway is closely correlated with the shedding of MVs from microglia in neuropathic pain, and MVs had a significant effect on neuropathic pain by participating in the interaction between microglia and neurons.

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“…Recent studies have shown that heterotypic adhesion of MC to activated but not resting T cells induces MC degranulation and cytokine production in a pathway associated with the activation of Ras and the MAPK signaling pathway [1,2,3,4,5]. …”

Section: Discussionmentioning

confidence: 99%

“…The human LAD2 MC were maintained in StemPro-34® SFM (GIBCO™ Invitrogen Corp., Grand Island, NY, USA) supplemented with 2 m M L -glutamine, 50 μg/mL streptomycin, 100 IU/mL penicillin, and 100 ng/mL recombinant human stem cell factor (SCF, PeproTech Asia, Rehovot, Israel) as previously described [6]. Primary cultured human cord blood MC were derived from human cord blood mononuclear cells in the presence of SCF, IL-6, and prostaglandin E 2 , and used as previously described [4]. …”

Section: Methodsmentioning

confidence: 99%

“…The close physical proximity between MC and T cells seen in inflamed tissues has led investigators to propose a bidirectional interaction between these 2 cell populations [1]. We have previously shown that direct contact with activated but not resting T cells, or their membranes or microvesicles, resulted in MC degranulation and the production of various cytokines such as IL-8, oncostatin M (OSM) and IL-24 [1,2,3,4]. This pathway is also associated with the activation of ERK and p38 [5].…”

Section: Introductionmentioning

confidence: 99%

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The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation

Salamon

Shefler

Hershko

et al. 2016

Int Arch Allergy Immunol

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Background: It has recently been reported that mast cells (MC) can be activated to degranulate and release certain cytokines in response to direct physical contact with activated but not resting T cells or their membranes. The MAPK family members ERK and p38 were found to participate. In this work, we further characterize the signaling events involved in this novel pathway of activation. Methods: Human MC were stimulated by activated T cell membranes (T*m). Phosphorylation of kinases was assessed by Western blotting. Protein kinase D (PKD) translocation was visualized by confocal microscopy. Degranulation was assessed by β-hexosaminidase release and cytokine production by ELISA. Results: Stimulation of human MC by activated T*m resulted in the activation of PKD. PKD inhibition by the specific pharmacological inhibitor Gö6976 resulted in a reduction in the phosphorylation of p38 but not ERK. Gö6976 also inhibited degranulation and cytokine release. Conclusions: MC stimulation by physical contact with T cells results in PKD activation, leading to the phosphorylation of p38, degranulation and release of cytokines. Understanding the molecular events associated with T cell-induced MC activation might lead to therapeutic approaches for controlling T cell-mediated inflammatory processes in which MC participate.

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T cell–derived microvesicles induce mast cell production of IL-24: Relevance to inflammatory skin diseases

Cited by 71 publications

References 33 publications

The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells

The pattern of IL-24/mda-7 and its cognate receptors expression following activation of human hepatic stellate cells

Microvesicles shed from microglia activated by the P2X7-p38 pathway are involved in neuropathic pain induced by spinal nerve ligation in rats

The Involvement of Protein Kinase D in T Cell-Induced Mast Cell Activation

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