Interplay between CXCR2 and BLT1 Facilitates Neutrophil Infiltration and Resultant Keratinocyte Activation in a Murine Model of Imiquimod-Induced Psoriasis

Sumida, Hitoshi; Yanagida, K.; Kita, Yoshiaki; Abe, Jun; Matsushima, Kouji; Nakamura, Motonao; Ishii, Satoshi; Sato, Shinichi; Shimizu, Takao

doi:10.4049/jimmunol.1302959

Cited by 129 publications

(95 citation statements)

References 50 publications

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“…A previous study demonstrated that neutrophil infiltration was considerably reduced in IMQ-induced dermatitis in Il1r1 KO mice (28). Interestingly, neutrophil depletion has been shown to ameliorate the severity of disease in this model of psoriasis (29), and clinical studies have demonstrated disease remission by drug-induced agranulocytosis, supporting a critical pathogenic role of neutrophils in psoriasis (30). We found that Il1r1 mRNA expression was significantly reduced in skin from the TTPΔARE mice, suggesting that decreased IL-1R1 signaling may have resulted in reduced dermal neutrophilic infiltration.…”

Section: Discussionmentioning

confidence: 80%

Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies

Patial

Curtis

Lai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that binds to adenylate-uridylate-rich elements (AREs) in the 3′-untranslated regions (3′UTRs) of specific mRNAs, such as that encoding TNF, and increases their rates of deadenylation and turnover. Stabilization of Tnf mRNA and other cytokine transcripts in TTP-deficient mice results in the development of a profound, chronic inflammatory syndrome characterized by polyarticular arthritis, dermatitis, myeloid hyperplasia, and autoimmunity. To address the hypothesis that increasing endogenous levels of TTP in an intact animal might be beneficial in the treatment of inflammatory diseases, we generated a mouse model (TTPΔARE) in which a 136-base instability motif in the 3′UTR of TTP mRNA was deleted in the endogenous genetic locus. These mice appeared normal, but cultured fibroblasts and macrophages derived from them exhibited increased stability of the otherwise highly labile TTP mRNA. This resulted in increased TTP protein expression in LPS-stimulated macrophages and increased levels of TTP protein in mouse tissues. TTPΔARE mice were protected from collagen antibody-induced arthritis, exhibited significantly reduced inflammation in imiquimod-induced dermatitis, and were resistant to induction of experimental autoimmune encephalomyelitis, presumably by dampening the excessive production of proinflammatory mediators in all cases. These data suggest that increased systemic levels of TTP, secondary to increased stability of its mRNA throughout the body, can be protective against inflammatory disease in certain models and might be viewed as an attractive therapeutic target for the treatment of human inflammatory diseases.AU-rich elements | mRNA stability | inflammation | deadenylation T ristetraprolin (TTP) is the prototype of a small family of RNA binding proteins that can bind to adenylate-uridylate (AU)-rich elements (AREs) in the 3′-UTR (3′UTR) of its target mRNAs and promote their rapid turnover (1, 2). TTP-deficient mice developed a chronic systemic inflammatory syndrome (3) that was prevented by interfering with the action of TNF (3-5). Tnf mRNA was then identified as a direct target of TTP-mediated destabilization (4, 6); its increase in stability in the TTP KO mice leads to the commensurate overproduction of TNF protein (4, 5).TTP mRNA expression exhibits a pattern characteristic of immediate-early response genes in several cell types, with low-toundetectable levels of expression under basal conditions, and a rapid and transient induction upon stimulation (4,7,8). The transient nature of this induction is largely due to the instability of the TTP mRNA itself, part of which is thought to be due to AREs located within the 3′UTR of TTP mRNA (4,8,9). Indeed, TTP has been suggested to bind to its own AREs and autoregulate its expression through a negative feedback loop (9). Although expression of TTP protein in these systems is also rapidly inducible, the protein is more stable than the mRNA after induction, often persisting at high level...

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Section: Discussionmentioning

confidence: 80%

Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies

Patial

Curtis

Lai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, we observed a marked reduction in neutrophil infiltration ( Figure 6, A and B; CD45 + /Ly6G + subset), a leukocyte subset also known to contribute to chronic skin inflammation in psoriasis (33).…”

Section: Anti-ccr6 Treatment Prevents Imq-induced Skin Inflammation Amentioning

confidence: 85%

Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice

Robert¹,

Ang²,

Sun³

et al. 2017

JCI Insight

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“…Chemokines and chemokine receptors function in a range of physiological processes, including cancer (41,42). In GC, CXC-chemokine receptor (CXCR) CXCR4 and CXCR2 were highly expressed in cancer tissues and predicted advanced tumor stage and poorer overall survival (43,44).…”

Section: Lymphangiogenesis and Metastasismentioning

confidence: 99%

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

Zhu

Hu²,

Wei

et al. 2018

Oncol Lett

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Abstract. Gastric cancer (GC) is one of the deadliest types of cancer in the world. Lymph node (LN) metastasis is a complex and malignant behavior of GC, involving a sequence of biological processes, including decreased adherence to adjacent cells, extracellular matrix (ECM) degradation and lymphatic channel permeation. LN metastasis is directly associated with the treatment response, local recurrence and long-term survival of patients with GC. Therefore, the molecular mechanisms of LN metastasis in GC development require further investigation. Recently, a large number of clinical studies have focused on the molecular mechanisms and biological markers of tumor invasion and metastasis. However, few articles have broadly summarized LN metastasis in GC, and the molecular mechanisms of LN metastasis are not yet fully understood. In the present review, the molecular mechanisms of LN metastasis in GC will be discussed, including the following aspects: Cell adhesion and movement, ECM degradation, new vessel formation, and molecular pattern differences between metastatic LNs and the primary tumor. This review may lead to a better understanding of LN metastasis in GC, and the identification of new diagnostic markers.

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Interplay between CXCR2 and BLT1 Facilitates Neutrophil Infiltration and Resultant Keratinocyte Activation in a Murine Model of Imiquimod-Induced Psoriasis

Cited by 129 publications

References 50 publications

Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies

Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies

Essential role for CCR6 in certain inflammatory diseases demonstrated using specific antagonist and knockin mice

Molecular background of the regional lymph node metastasis of gastric cancer (Review)

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