Influence of mizolastine on antigen-induced activation of signalling pathways in murine mast cells

Xia, Qingrong; Zhou, Wenting; Yang, Sherry; Zhang, S. Q.; Chen, B.; Wang, D. B.; Wang, Y.; Zhang, X. J.

doi:10.1111/j.1365-2230.2006.02050.x

Cited by 5 publications

(4 citation statements)

References 14 publications

(33 reference statements)

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“…In a previous report from this laboratory, impaired PI3K/Akt activation with increased TNF‐α was shown to reduce NF‐κB activation (26), which has been shown to be involved in the increase of apoptosis in keratinocytes in the depigmented compared to the normally pigmented epidermis in vitiligo (25). Because histamine has been shown to increase PI3K and Akt activation (36,37), it was expected that the histamine could increase the survival of vitiliginous keratinocytes, with an in vitro model that was prepared with cultured normal human keratinocytes in the presence of TNF‐α and wortmannin, a PI3K inhibitor. In fact, histamine, particularly the H2 receptor agonist, reduced the loss of vitiliginous keratinocytes (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…(*P < 0.05). been shown to increase PI3K and Akt activation (36,37), it was expected that the histamine could increase the survival of vitiliginous keratinocytes, with an in vitro model that was prepared with cultured normal human keratinocytes in the presence of TNF-a and wortmannin, a PI3K inhibitor. In fact, histamine, particularly the H2 receptor agonist, reduced the loss of vitiliginous keratinocytes (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival

Kim

Lee

2010

Experimental Dermatology

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Repigmention of vitiligo requires melanocyte proliferation and migration. Keratinocytes have been shown to play a role in this process. Data from this laboratory showed that bee venom (BV) stimulated melanocyte proliferation and migration as well as melanogenesis. As histamine release is associated with BV, its effect on melanocyte proliferation and migration was examined. Cultured normal human melanocytes treated with histamine were studied with and without receptor-specific antagonists or agonists. The effect of histamine on vitiliginous keratinocytes, in cultured cells treated with a PI3K inhibitor in the presence of TNF-α, was also examined. Histamine exerted a more significant effect on melanocyte proliferation than on melanogenesis. This occurred through the H2 receptor with complex signalling to ERK, CREB, and Akt activation, which stimulated melanocyte migration. Histamine and the H2 receptor agonist also increased survival of vitiliginous, but not normal, keratinocytes, with NF-κB activation. Because expression levels of the H2 receptor was significantly decreased in depigmented compared to normally pigmented epidermis, in patients with vitiligo, histamine may increase the survival of vitiliginous keratinocytes. Overall, histamine stimulated the proliferation and migration of melanocytes and the vitiliginous keratinocyte survival, providing the basis for novel therapeutic approaches to vitiligo repigmentation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival

Kim

Lee

2010

Experimental Dermatology

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“…Although the receptors and signaling pathway of these antihistamines in vertebrates such as humans are already known, the detailed mechanisms in marine invertebrates remain unknown. As mizolastine affects both the generation and release process of many cytokines in cells, targeting signaling pathways, inhibiting inflammation-induced activity, and exhibiting anti-angiogenesis properties (Carayol et al 2002;Xia et al 2005Xia et al , 2006, a promising research direction should involve linking its substantial and reversible anti-settlement activity with its known biochemical functions, and further, possibly clarifying the biochemical regulation of biofouling.…”

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confidence: 99%

Reversible anti-settlement activity againstAmphibalanus(=Balanus)amphitrite, Bugula neritina, andHydroides elegansby a nontoxic pharmaceutical compound, mizolastine

et al. 2009

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Mizolastine, an antihistamine pharmaceutical, was found to significantly inhibit larval settlement of the barnacle Amphibalanus (=Balanus) amphitrite, the bryozoan Bugula neritina, and the polychaete Hydroides elegans with EC(50) values of 4.2, 11.2, and 4.1 microg ml(-1), respectively. No toxicity against the larvae of these three species was observed at the concentration range tested during incubations with mizolastine. To determine whether the anti-settlement activity of mizolastine is reversible, recovery bioassays using these three species were conducted. More than 70% of the larvae that had been exposed for 4 h to mizolastine at concentrations four-fold greater than their respective EC(50) values completed normal metamorphosis. The results of the recovery bioassay provide evidence that the anti-settlement effect of mizolastine is reversible in addition to being nontoxic. The anti-settlement activities of several intermediates of the synthesis process of mizolastine were also examined. One of the intermediates, 2-chloro-1-(4-fluorobenzyl)-1H-benzo[d]imidazole, inhibited larval settlement and metamorphosis with low toxicity. These results may improve the understanding of the key functional group responsible for the anti-settlement activity of mizolastine.

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“…In contrast, most studies have suggested that phosphoinositide 3-kinase, and not p38 MAPK, is responsible for activation of Akt isoforms. Other data suggest that MAPK activation may inhibit Akt activation (20 -22), particularly in intestinal epithelia, or that Akt activation can lead to p38 MAPK activation (23,24). Thus, while existing data suggest that a relationship between p38 MAPK and Akt exists in many systems, the intermediates involved in this process, and even the direction of the effect, are controversial.…”

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confidence: 99%

MAPKAPK-2 Is a Critical Signaling Intermediate in NHE3 Activation Following Na+-Glucose Cotransport

Wang

Graham

et al. 2006

Journal of Biological Chemistry

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Villus enterocyte nutrient absorption occurs via precisely orchestrated interactions among multiple transporters. For example, transport by the apical Na ؉ -glucose cotransporter, SGLT1, triggers translocation of NHE3, Na ؉ -H ؉ antiporter isoform 3, to the plasma membrane. This translocation requires activation of p38 mitogen-activated protein kinase (MAPK), Akt2, and ezrin. Akt2 directly phosphorylates ezrin, but the precise role of p38 MAPK in this process remains to be defined. Sequence analysis suggested that p38 MAPK could not directly phosphorylate Akt2. We hypothesized that MAPKAPK-2 might link p38 MAPK and Akt2 activation. MAPKAPK-2 was phosphorylated after initiation of Na ؉ -glucose cotransport with kinetics that paralleled activation of p38 MAPK, Akt2, and ezrin. MAPKAPK-2, Akt2, and ezrin phosphorylation were all attenuated by p38 MAPK inhibition but were unaffected by dominant negative ezrin expression. Akt2 inhibition blocked ezrin but not p38 MAPK or MAPKAPK-2 phosphorylation, suggesting that MAPKAPK-2 could be an intermediate in p38 MAPK-dependent Akt2 activation. Consistent with this, MAP-KAPK-2 could phosphorylate an Akt2-derived peptide in vitro. siRNA-mediated MAPKAPK-2 knockdown inhibited phosphorylation of Akt2 and ezrin but not p38 MAPK. MAPKAPK-2 knockdown also blocked NHE3 translocation. Thus, MAP-KAPK-2 controls Akt2 phosphorylation. In so doing, MAP-KAPK-2 links p38 MAPK to Akt2, ezrin, and NHE3 activation after SGLT1-mediated transport.Intestinal nutrient absorption occurs via precisely orchestrated regulation of multiple transporters. One critical example involves coordinated Na ϩ and glucose absorption by villus enterocytes (1, 2). This process may, in part, explain why inclusion of Na ϩ and glucose in oral rehydration solutions used to treat life-threatening diarrheal disease augments therapeutic efficacy (3, 4). In mechanistic terms, Na ϩ -glucose cotransport mediated by SGLT1 leads to activation of the apical Na ϩ -H ϩ antiporter NHE3. This generates a favorable osmotic gradient that drives transepithelial water absorption (5, 6). Coordination of SGLT1 and NHE3 involves a complex signal transduction pathway where activation of p38 mitogen-activated protein kinase (MAPK) 2 leads to Akt2 activation, ezrin phosphorylation, and NHE3 translocation to the brush border (1,7,8).Although it is clear that p38 MAPK is critical to this process (1), the mechanisms by which p38 MAPK activates Akt2 are unknown. Available data suggest that p38 MAPK cannot activate Akt2 directly. We therefore considered p38 MAPK effectors as potential signaling intermediates in this process.A large number of kinases have been reported to be p38 MAPK effectors, including Mnk1, Mnk2, PRAK, MEF2, ATF-2, Stat1, and MAPK-activated protein kinase-2 (MAPKAPK-2) (9, 10). These, in turn, act on additional substrates, including CREB and HSP27 (11-17). Among these effectors, two recent reports suggest that MAPKAPK-2, a serine/threonine protein kinase, may link p38 MAPK and Akt. These studies showed that recombinant MAPKAPK...

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Influence of mizolastine on antigen-induced activation of signalling pathways in murine mast cells

Abstract: PKC-mediated phosphorylation of Akt can be blocked by mizolastine. There may be a PKC-independent pathway effectively activating MAPK pathways in mast cells in response to antigen induction, which cannot be affected by mizolastine.

Cited by 5 publications

References 14 publications

Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival

Histamine effect on melanocyte proliferation and vitiliginous keratinocyte survival

Reversible anti-settlement activity againstAmphibalanus(=Balanus)amphitrite, Bugula neritina, andHydroides elegansby a nontoxic pharmaceutical compound, mizolastine

MAPKAPK-2 Is a Critical Signaling Intermediate in NHE3 Activation Following Na+-Glucose Cotransport

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