Glucocorticoids inhibit degranulation of mast cells in allergic asthma via nongenomic mechanism

Zhou, Jian; Liu, D.-F.; Liu, C.; Kang, Zhiming; Shen, Xiao-Liang; Chen, Y.-Z.; Xu, Tao; Jiang, Chun‐Lei

doi:10.1111/j.1398-9995.2008.01725.x

Cited by 63 publications

(39 citation statements)

References 34 publications

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“…, we verified modulation of Ca 2? signaling might play an key role in the non-genomic action of GCs [12]. Regrettably, the study showed that cAMP was not involved in the rapid effect of the novel GCs (HG).…”

Section: Discussionmentioning

confidence: 99%

“…plus 1 ml of suspension (10 mg ovalbumin in saline, i.m.). Then, 30 days later, animals were challenged to allergic asthma reaction with an aerosol of antigen (ovalbumin suspended in saline, 10 mg/ml) for 25 s [12]. In addition, the pulmonary function parameters were monitored continuously.…”

Section: Allergic Reaction Modelmentioning

confidence: 99%

“…Mifepristone (RU486) is an antagonist of classic glucocorticoid receptor, which could exclude the traditional genomic mechanism mediated by glucocorticoid receptor [12,26,27]. The sensitized cells were preincubated with RU486 at 10 -6 M for 30 min, and then incubated with HG (10 -7 M) for 7 min before antigen was added.…”

Section: Non-genomic Effects Of Hg On Histamine Release From Mast Cellsmentioning

confidence: 99%

“…It has been reported that GCs could rapidly inhibit Lck and Fyn kinases in human lymphocytes to exert immunosuppressive effects via non-genomic mechanism [9,10]. Our recent studies have shown that GCs could inhibit degranulation of mast cells and neutrophils, phagocytosis of macrophages via non-genomic mechanism, to exert immunosuppressive, anti-allergic and antiinflammatory effects [11][12][13][14]. However, there have still been few reports about novel drugs based on the knowledge of GCs' non-genomic effects.…”

mentioning

confidence: 99%

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A novel strategy for development of glucocorticoids through non-genomic mechanism

Zhou

Sheng

et al. 2010

Cell. Mol. Life Sci.

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Glucocorticoids (GCs) are routinely believed to take effect through genomic mechanisms, which are also largely responsible for GCs' side effects. Beneficial non-genomic effects of GCs have been reported as being independent of the genomic pathway. Here, we synthesized a new type of GCs, which took effect mainly via non-genomic mechanisms. Hydrocortisone was conjugated with glycine, lysine and phenylalanine to get a bigger molecular structure, which could hardly go through the cell membrane. Evaluation of the anti-inflammatory efficacy showed that hydrocortisone-conjugated glycine (HG) and lysine could inhibit neutrophil degranulation within 15 min. HG could inhibit IgE-mediated histamine release from mast cells via a non-genomic pathway, and rapidly alleviate allergic reaction. Luciferase reporter assay showed that HG would not activate the glucocorticoid response element within 30 min, which verified the rapid effects independent of the genomic pathway. The work proposes a novel insight into the development of novel GCs, and provides new tools for experimental study on non-genomic mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Allergic Reaction Modelmentioning

confidence: 99%

Section: Non-genomic Effects Of Hg On Histamine Release From Mast Cellsmentioning

confidence: 99%

mentioning

confidence: 99%

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A novel strategy for development of glucocorticoids through non-genomic mechanism

Zhou

Sheng

et al. 2010

Cell. Mol. Life Sci.

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“…Several studies have reported that glucocorticoids may have an indirect anti-inflammatory impact on MCs, with the postulated mechanism being a reduction of stem cell factor production by fibroblasts ( Da Silva et al ., 2002). Alternatively, they may also have direct impacts by reducing IgE binding to the FcεRI receptors, thereby down regulating the expression of these receptors on the cell membrane of the MCs and inhibiting MC degranulation in vitro ( Finotto et al ., 1997; Yamaguchi et al ., 2001; Zhou et al ., 2008). Prior to the current study, the only report of expression of GR in human MCs was from Oppong et al .…”

Section: Discussionmentioning

confidence: 99%

Immunoprofiling of human uterine mast cells identifies three phenotypes and expression of ERβ and glucocorticoid receptor

et al. 2017

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Background: Human mast cells (MCs) are long-lived tissue-resident immune cells characterised by granules containing the proteases chymase and/or tryptase. Their phenotype is modulated by their tissue microenvironment. The human uterus has an outer muscular layer (the myometrium) surrounding the endometrium, both of which play an important role in supporting a pregnancy. The endometrium is a sex steroid target tissue consisting of epithelial cells (luminal, glandular) surrounded by a multicellular stroma, with the latter containing an extensive vascular compartment as well as fluctuating populations of immune cells that play an important role in regulating tissue function. The role of MCs in the human uterus is poorly understood with little known about their regulation or the impact of steroids on their differentiation status. The current study had two aims: 1) To investigate the spatial and temporal location of uterine MCs and determine their phenotype; 2) To determine whether MCs express receptors for steroids implicated in uterine function, including oestrogen (ERα, ERβ), progesterone (PR) and glucocorticoids (GR). Methods: Tissue samples from women (n=46) were used for RNA extraction or fixed for immunohistochemistry. Results: Messenger RNAs encoded by TPSAB1 (tryptase) and CMA1 (chymase) were detected in endometrial tissue homogenates. Immunohistochemistry revealed the relative abundance of tryptase MCs was myometrium>basal endometrium>functional endometrium. We show for the first time that uterine MCs are predominantly of the classical MC subtypes: (positive, +; negative, -) tryptase+/chymase- and tryptase+/chymase+, but a third subtype was also identified (tryptase-/chymase+). Tryptase+ MCs were of an ERβ+/ERα-/PR-/GR+ phenotype mirroring other uterine immune cell populations, including natural killer cells. Conclusions: Endometrial tissue resident immune MCs have three protease-specific phenotypes. Expression of both ERβ and GR in MCs mirrors that of other immune cells in the endometrium and suggests that MC function may be altered by the local steroid microenvironment.

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Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells

Shrestha¹,

Wershil²,

Sarwark³

et al. 2010

Arthritis & Rheumatism

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Objective To investigate the distribution of mast cells and dendritic cell (DC) subsets in paired muscle and skin (lesional/nonlesional) from untreated children with juvenile dermatomyositis (DM). Methods Muscle and skin biopsy samples (4 skin biopsy samples with active rash) from 7 patients with probable/definite juvenile DM were compared with muscle and skin samples from 10 healthy pediatric controls. Mast cell distribution and number were assessed by toluidine blue staining and analyzed by Student’s t-test. Immunohistochemical analysis was performed to identify mature DCs, myeloid DCs (MDCs), and plasmacytoid DCs (PDCs) by using antibodies against DC-LAMP, blood dendritic cell antigen 1 (BDCA-1), and BDCA-2, respectively. Myxovirus resistance protein A (MxA) staining indicated active type I interferon (IFN) signaling; positive staining was scored semiquantitatively and analyzed using the Mann-Whitney U test. Results Both inflamed and nonlesional skin from patients with juvenile DM contained more mast cells than did skin from pediatric controls (P = 0.029), and comparable numbers of mast cells were present in lesional and nonlesional skin. Interestingly, mast cell numbers were greater in skin than in paired muscle tissue from patients with juvenile DM (P = 0.014) and were not increased in muscle from patients with juvenile DM compared with control muscle. Both muscle and skin from patients with juvenile DM showed more mature PDCs and MxA staining than did their corresponding control tissues (P < 0.05). In both muscle and skin from patients with juvenile DM and in pediatric control muscle, there were fewer MDCs than PDCs, and the distributions of MDCs and PDCs were similar in pediatric control skin samples. Conclusion The identification of mast cells in skin (irrespective of rash) from patients with juvenile DM, but not in paired muscle tissue, suggests that they have a specific role in juvenile DM skin pathophysiology. In skin from patients with juvenile DM, increased numbers of PDCs and increased expression of type I IFN–induced protein suggest a selective influence on T cell differentiation and subsequent effector function.

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Glucocorticoids inhibit degranulation of mast cells in allergic asthma via nongenomic mechanism

Abstract: The study suggested for the first time that nongenomic pathway was involved in GCs' rapid inhibition on allergic asthma, and raised the possibility of new therapeutic strategies for allergic diseases including asthma.

Cited by 63 publications

References 34 publications

A novel strategy for development of glucocorticoids through non-genomic mechanism

A novel strategy for development of glucocorticoids through non-genomic mechanism

Immunoprofiling of human uterine mast cells identifies three phenotypes and expression of ERβ and glucocorticoid receptor

Lesional and nonlesional skin from patients with untreated juvenile dermatomyositis displays increased numbers of mast cells and mature plasmacytoid dendritic cells

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