CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9

Chabot, Valérie; Reverdiau, Pascale; Iochmann, Sophie; Rico, Angélique; Sénécal, Delphine; Goupille, Caroline; Sizaret, P; Sensebé, Luc

doi:10.1189/jlb.0804464

Cited by 55 publications

(36 citation statements)

References 62 publications

(62 reference statements)

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“…The role of MMP-9 in DC migration to inflammatory sites, draining lymph nodes, and out of brain capillaries has been demonstrated previously. [24][25][26] Similar to other immune cells, DCs express CB2R 27,28 (and present study). Cannabinoids were shown to reduce the stimulatory capacity of DCs for T cells, to inhibit the production of proinflammatory cytokines (IL-6, IFN-␥, and IL-17), and chemokines (CCL2 and -3), and to up-regulate IL-10 production in DC-T cell cocultures (reviewed in Basu and Dittel 4 ).…”

Section: Introductionsupporting

confidence: 79%

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

Adhikary¹,

Kocieda

Yen

et al. 2012

Blood

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Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and autoimmune disease and CNS injury models results in significant attenuation of clinical disease, and reduction of inflammatory mediators. Previous studies reported that CB2R signaling also reduces leukocyte migration. Migration of dendritic cells (DCs) to various sites is required for their activation and for the initiation of adaptive immune responses. Here, we report for the first time that CB2R signaling affects DC migration in vitro and in vivo, primarily through the inhibition of matrix metalloproteinase 9 (MMP-9) expression. Reduced MMP-9 production by DCs results in decreased migration to draining lymph nodes in vivo and in vitro in the matrigel migration assay. The effect on Mmp-9 expression is mediated through CB2R, resulting in reduction in cAMP levels, subsequent decrease in ERK activation, and reduced binding of c-Fos and c-Jun to Mmp-9 promoter activator protein 1 sites. We postulate that, by dampening production of MMP-9 and subsequent MMP-9-dependent DC migration, cannabinoids contribute to resolve acute inflammation and to reestablish homeostasis. Selective CB2R agonists might be valuable future therapeutic agents for the treatment of chronic inflammatory conditions by targeting activated immune cells, including DCs. IntroductionThe cannabinoid system consists of cannabinoid receptors and their ligands, including endocannabinoids, synthetic cannabinoid receptor agonists and antagonists, and phytocannabinoids. Several cannabinoid receptors have been described, that is, the classic cannabinoid receptor 1 (GPR) and GPR, the previously orphaned G-protein receptors GPR18 and GPR55, various ion channels, and intracellular peroxisome proliferator-activated receptor-␥ (reviewed in Pertwee et al 1 and Console-Bram 2 ). The 2 classic cannabinoid receptors, CB1R and CB2R, have different distribution and functions (reviewed in Kubajewska and Constantinescu 3 and Basu and Dittel 4 ). CB1R is abundantly expressed on CNS and peripheral neurons and involved in neural functions. In contrast, CB2R is mostly expressed on immune cells and involved in immunoregulation. Administration of CB2R-selective agonists in models of inflammatory and autoimmune diseases such as systemic sclerosis, experimental autoimmune uveoretinitis, inflammatory bowel diseases, and experimental autoimmune encephalomyelitis (EAE) resulted in attenuation of clinical disease (reviewed in Basu and Dittel 4 ). CB2R agonists also have been reported to have a beneficial effect in models of CNS injury such as cerebral infarction and spinal cord injury. [5][6][7][8] In addition to effects on clinical outcome, CB2R agonists reduced the levels of inflammatory mediators in various experimental models. [8][9][10] A possible mechanism for the anti-inflammatory effect of CB2R signaling is the direct action of CB2R agonists on immune cells. In vitro studies indicated that CB2R signaling inhibited the production of proinflammatory cytokines such as TNF␣, IL-6, IL-2, and IFN-␥ by ac...

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Section: Introductionsupporting

confidence: 79%

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

Adhikary¹,

Kocieda

Yen

et al. 2012

Blood

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“…The role of MMP-9 in DC migration both in response to proinflammatory chemokines such as CCL5 and lymph node-derived chemokines such as CCL19 has been demonstrated in vitro, in skin explant models, and in vivo following epicutaneous hapten stimulation and treatment with anti-MMP-9 Abs, as well as in MMP-9-deficient mice. 18,[20][21][22][23][24][25] Recently, DC transmigration through brain capillary endothelial cell monolayers also has been shown to depend on MMPs. 26 In addition, DCs from multiple sclerosis (MS) patients have been shown to secrete high levels of MMP-2, -3, and -9 and to exhibit increased spontaneous migration over ECM-coated filters.…”

Section: Discussionmentioning

confidence: 99%

PGE2-induced metalloproteinase-9 is essential for dendritic cell migration

Yen

Khayrullina

Ganea

2008

Blood

137

143

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Following antigen acquisition and maturation, dendritic cells (DCs) disengage from the extracellular matrix, cross basement membranes, and travel to draining lymph nodes to activate T cells. CCR7 expression is necessary but not sufficient for the directional migration of DCs. Prostaglandin E2 (PGE2), present in inflammatory sites, induces DC migration, presumably by enacting a migration-permissive gene expression program. Since regulation of DC migration is highly important for their use in vaccination and therapy, we examined the PGE2-induced changes in the expression of metalloproteinases (MMPs). Our results indicate that PGE2 significantly up-regulates MMP-9 expression, induces both secreted and membrane-bound MMP-9, and that in turn, DC-derived MMP-9 is essential for DC chemotaxis in response to the CCR7 ligand CCL19, Matrigel migration, and in vivo migration in both wild-type and MMP-9-deficient hosts. We conclude that DCs matured within inflammatory sites require both CCR7 and PGE2-induced MMP-9 for their directional migration to draining lymph nodes. (Blood. 2008;111: 260-270)

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“…Entretanto, outros trabalhos mostram que somente a MMP-9, mas não a MMP-2, está expressa nas células dendríticas imaturas e maturas, nas formas pró e ativa, respectivamente (CHABOT et al, 2006). Além disso, a deleção do gene da MMP-9 afeta a transmigração das células dendríticas pulmonares no lúmen das vias aéreas, sem, no entanto alterar a migração para os linfonodos torácicos (VERMAELEN et al, 2003).…”

Section: Discussionunclassified

“…Existem inúmeros fatores que regulam a produção das metaloproteinases de matriz e dos seus inibidores. Estudos recentes mostraram que a quimiocina CCL5 regula a liberação e expressão da MMP-9 nas células dendríticas, pórem não apresenta nenhum efeito na expressão da MMP-2 (CHABOT et al, 2006).…”

Section: Discussionunclassified

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Avaliação do papel da nattectina, toxina do veneno de Thalassophryne nattereri, na respota imune inata e específica.

Saraiva¹

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RESUMOO objetivo deste trabalho foi avaliar a resposta imune inata induzida pela Nattectina, uma lectina tipo C isolada do veneno de Thalassophryne nattereri, em um modelo de inflamação murina e subseqüentemente seu papel na ativação das células dendríticas e indução da resposta imune específica. Nossos resultados mostram que a Nattectina induziu uma reação inflamatória na cavidade peritoneal de camundongos BALB/c caracterizada pelo influxo predominante de neutrófilos em 1 e 6 horas, substituído por macrófagos em 24 horas. Análises do sobrenadante da suspensão celular da cavidade peritoneal mostraram que a Nattectina induziu a liberação de mediadores inflamatórios como LTB 4 e PGE 2 em 6 horas, IL-1β em 1 e 6 h, IL-6 em 1 h, MCP-1 em 1 e 24 h e KC em 1 h. Além disso, IL-12p70 foi observada no peritônio em 1 e 24 h e IL-10 em 6 e 24 h. Células dendríticas imaturas de origem mieloíde (CD11b high CD11c high B220 low ) foram amadurecidas pela Nattectina com aumento na expressão das moléculas MHC de classe II e das coestimulatórias CD40, CD80 e CD86 e expressão de metaloproteinases de matriz MMP-2 e MMP-9, com síntese de IL-10 e IL-12p70. As células dendríticas imaturas apresentaram grande capacidade de captura e apresentação da Nattectina. Como conseqüência da ativação das células dendríticas, a Nattectina foi capaz de desencadear uma reposta imune adaptativa caracterizada pela ativação preferencial de linfócitos Th1, com síntese de IFN-γe de IL-10, favorecendo a produção de IgG2a específica. A presença de IL-10 pode ser responsável pela limitação da inflamação patológica induzida pelo veneno de T. nattereri e pela manutenção da inflamação crônica não resolvida observada no envenenamento. Finalmente, a Nattectina é um potente candidato antigênico juntamente com as células dendríticas para uso em imunoterapias.PDF Creator: PDF4U Pro DEMO Version. If you want to remove this line, please purchase the full version ABSTRACTRecently, it was identified a C-type lectin in the venom of Thalassophryne nattereri fish named Nattectin. In this study, we investigated the innate and adquired immune responses induced by Nattectin and consequently its role in the dendritic cell activation. The toxin was i.p. injected in BALB/c mice for evaluation of cellular recruitment and inflammatory mediators, antibody and cytokine production. Dendritic cells obtained after bone marrow cell culture with GM-CSF for 7d were stimulated with Nattectin for 24h. The expression of surface molecules and MMPs were analyzed by FACS and immunohistochemistry, respectively. Nattectin induced a significant cellular recruitment into peritoneal cavity, mainly neutrophils at 1 and 6hfollowed by macrophages at 24h. One hour after the Nattectin injection the levels of IL-6, IL-1β, MCP-1 and KC were detected, however in 6 or 24h only IL-1β and IL-10 or MCP-1 and IL-12p70 were determined, respectively. Nattectin induced the PGE 2 and LTB 4 synthesis at 6h. After immunization, mice produced elevated levels of anti- immune response that might be related to its activit...

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CCL5-enhanced human immature dendritic cell migration through the basement membrane in vitro depends on matrix metalloproteinase-9

Cited by 55 publications

References 62 publications

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

PGE2-induced metalloproteinase-9 is essential for dendritic cell migration

Avaliação do papel da nattectina, toxina do veneno de Thalassophryne nattereri, na respota imune inata e específica.

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