Tryptase activates peripheral blood mononuclear cells causing the synthesis and release of TNF-α, IL-6 and IL-1β: possible relevance to multiple sclerosis

Malamud, Vivian; Vaaknin, Ady; Abramsky, Oded; Mor, Michal; Burgess, Laurence E.; Ben‐Yehudah, Ahmi; Lorberboum-Galski, Haya

doi:10.1016/s0165-5728(03)00090-0

Cited by 59 publications

(48 citation statements)

References 45 publications

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“…In addition, tryptase can stimulate human endothelial cells for increased production of MCP-1 and IL-8 [24, 25, 91], chemokines which can attract neutrophils and many other cells of the immune system. Furthermore, tryptase activates peripheral blood mononuclear cells for TNF-, IL-6 and IL-1 production [109], human neutrophils for IL-8 secretion [197], and human T cells for IL-6 release [101]. Activation of these cells is very likely mediated via activation of the proteinase-activated receptor-2 (PAR-2) by tryptase.…”

Section: Mast Cell Serine Proteinases In Psoriasismentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

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Mast cells have traditionally been considered as eVector cells in allergy but during the last decade it has been realized that mast cells are essentially involved in the mechanisms of innate and acquired immunity. Upon activation by anaphylactic, piecemeal degranulation or degranulation-independent mechanisms mast cells can secrete rapidly or slowly a number of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express cell surface co-stimulatory receptors and ligands, and they can express MHC class II molecules and thereby present antigens. These soluble factors and cell surface molecules can interact with other cells, such as endothelial cells, keratinocytes, sensory nerves, neutrophils, T cell subsets and antigen presenting cells which are essential eVectors in the development of skin inXammation. Besides promoting inXammation, mast cells may attempt in some circumstances to suppress the inXammation and epidermal growth but the regulation between suppressive and proinXammatory mechanisms is unclear. Psoriasis is characterized by epidermal hyperplasia and chronic inXammation where tryptase-and chymase-positive MC TC mast cells are activated early in the developing lesion and later the cells increase in number in the upper dermis with concomitant expression of cytokines and TNF superfamily ligands as well as increased contacts with neuropeptide-containing sensory nerves. Due to the intimate involvement of mast cells in immunity and chronic inXammation the role of mast cells in psoriasis is discussed in this review.

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Section: Mast Cell Serine Proteinases In Psoriasismentioning

confidence: 99%

Is there a role for mast cells in psoriasis?

et al. 2008

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“…Mast cell tryptase is a major secretory protein of human mast cells, which is elevated in the CSF of patients with multiple sclerosis (MS) [3]. It can stimulate peripheral mononuclear cells to secrete TNF-alpha and IL-6 [4], as well as activate PAR-2 to induce widespread inflammation [5].…”

Section: Introductionmentioning

confidence: 99%

Mast Cell Tryptase Induces Microglia Activation via Protease-activated Receptor 2 Signaling

Zhang

Zeng

Yang

et al. 2012

Cell Physiol Biochem

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Background: Mast cell tryptase can stimulate peripheral mononuclear cells activation to cause widespread inflammation. However, the influence of tryptase on microglia, the resident immune cells in the brain, remains uninvestigated. Since microglia plays a pivotal role in immune surveillance of CNS, we studied the effect of tryptase on microglia activation. Methods: Induction of microglia activation by tryptase was examined with primary cultured microglia. TNF-alpha and IL-6 was measured with a commercial ELISA kit. Intracellular ROS was determined by dichlorodihydrofluorescein oxidation. Mitochondrial membrane potential was assessed with the MitoProbe^TM JC-1 assay kit. And MAPK and NF-kappa B phosphorylation were evaluated by Western blot. Results: We found that tryptase stimulated microglia activation and subsequently produced proinflammatory factors TNF-alpha, IL-6 and ROS. Inhibition of PAR-2 activation reduced tryptaseinduced TNF-alpha, IL-6 and ROS production, and mitochondrial membrane potential loss in microglia. Among the three members of MAPK pathway, ERK and p38, but not JNK mediated tryptase-induced microglia activation. Inhibition of PAR-2 suppressed tryptase-induced ERK and p38 MAPK pathway activation in microglia. Tryptase also activated NF-kappa B within 30 min, and ammonium pyrrolidinedithiocarbamate, an inhibitor of NF- kappa B, reduced tryptase-induced TNF-alpha and IL-6 release. Conclusions: Our results suggest that tryptase can induce microglia activation and pro-inflammatory mediator release via PAR-2-MAPK-NF-kappa B signaling pathway, which will contribute to the development of microglia-mediated inflammation in brain.

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“…Tryptase stimulates endothelial cells to synthesize and release IL-1β and IL-8 that induce leukocyte infiltration (van Haelst et al, 2001;Compton et al, 1998). Tryptase can also activate peripheral blood mononuclear cells to produce and secrete IL-6 and TNF-α (Malamud et al, 2003), so as to affect the occurrence and development of inflammation in vascular system. The proteinase-activated receptor 2 (PAR-2) on multiplicate cells can be activated by tryptase to react on its physiological roles.…”

Section: Discussionmentioning

confidence: 99%

Effects of RNA interference-induced tryptase down-regulation in P815 cells on IL-6 and TNF-α release of endothelial cells

Jiang

Zhao

et al. 2008

J. Zhejiang Univ. Sci. B

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Abstract:Objective: To explore the effects of down-regulated tryptase expression in mast cells on the synthesis and release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) of vascular endothelial cells. Methods: Tryptase-siRNA (small-interfering RNA) vector was constructed to inhibit tryptase expression in P815 cells. The medium of P815 cells treated by the tryptase-siRNA (RNAi-P815 group) or pure vector (P815 group) was collected and used to culture bEnd.3 cells. The messenger RNAs (mRNAs) of IL-6 and TNF-α in bEnd.3 cells and their protein levels in the medium were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: IL-6 and TNF-α mRNAs in bEnd.3 cells cultured in RNAi-P815-conditioned medium decreased significantly compared to those in P815-conditioned medium. Consistently, IL-6 and TNF-α protein levels in the medium of bEnd.3 of RNAi-P815 group were lower than those of P815 group. Conclusion: Reduced tryptase expression significantly inhibited the synthesis and release of IL-6 and TNF-α in vascular endothelial cells. RNA interference targeting tryptase expression may be a new anti-inflammatory strategy for vascular diseases.

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Tryptase activates peripheral blood mononuclear cells causing the synthesis and release of TNF-α, IL-6 and IL-1β: possible relevance to multiple sclerosis

Cited by 59 publications

References 45 publications

Is there a role for mast cells in psoriasis?

Is there a role for mast cells in psoriasis?

Mast Cell Tryptase Induces Microglia Activation via Protease-activated Receptor 2 Signaling

Effects of RNA interference-induced tryptase down-regulation in P815 cells on IL-6 and TNF-α release of endothelial cells

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