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Background and purpose: Chemokines orchestrate neutrophil recruitment to inflammatory foci. In the present study, we evaluated the participation of three chemokines, KC/CXCL1, MIP-2/CXCL2 and LIX/CXCL5, which are ligands for chemokine receptor 2 (CXCR2), in mediating neutrophil recruitment in immune inflammation induced by antigen in immunized mice. Experimental approach: Neutrophil recruitment was assessed in immunized mice challenged with methylated bovine serum albumin, KC/CXCL1, LIX/CXCL5 or tumour necrosis factor (TNF)-a. Cytokine and chemokine levels were determined in peritoneal exudates and in supernatants of macrophages and mast cells by ELISA. CXCR2 and intercellular adhesion molecule 1 (ICAM-1) expression was determined using immunohistochemistry and confocal microscopy. Key results: Antigen challenge induced dose-and time-dependent neutrophil recruitment and production of KC/CXCL1, LIX/CXCL5 and TNF-a, but not MIP-2/CXCL2, in peritoneal exudates. Neutrophil recruitment was inhibited by treatment with reparixin (CXCR1/2 antagonist), anti-KC/CXCL1, anti-LIX/CXCL5 or anti-TNF-a antibodies and in tumour necrosis factor receptor 1-deficient mice. Intraperitoneal injection of KC/CXCL1 and LIX/CXCL5 induced dose-and time-dependent neutrophil recruitment and TNF-a production, which were inhibited by reparixin or anti-TNF-a treatment. Macrophages and mast cells expressed CXCR2 receptors. Increased macrophage numbers enhanced, while cromolyn sodium (mast cell stabilizer) diminished, LIX/CXCL5-induced neutrophil recruitment. Macrophages and mast cells from immunized mice produced TNF-a upon LIX/CXCL5 stimulation. Methylated bovine serum albumin induced expression of ICAM-1 on mesenteric vascular endothelium, which was inhibited by anti-TNF-a or anti-LIX/CXCL5. Conclusion and implications: Following antigen challenge, CXCR2 ligands are produced and act on macrophages and mast cells triggering the production of TNF-a, which synergistically contribute to neutrophil recruitment through induction of the expression of ICAM-1.

IL-23/IL-17-induced neutrophil recruitment plays a pivotal role in rheumatoid arthritis (RA). However, the mechanism of the neutrophil recruitment is obscure. Here we report that prostaglandin enhances the IL-23/IL-17-induced neutrophil migration in a murine model of RA by inhibiting IL-12 and IFN γ production. Methylated BSA (mBSA) and IL-23-induced neutrophil migration was inhibited by anti-IL-23 and anti-IL-17 antibodies, COX inhibitors, IL-12, or IFNγ but was enhanced by prostaglandin E 2 (PGE 2 ). IL-23-induced IL-17 production was increased by PGE 2 and suppressed by COX-inhibition or IL-12. Furthermore, COX inhibition failed to reduce IL-23-induced neutrophil migration in IL-12- or IFNγ-deficient mice. IL-17-induced neutrophil migration was not affected by COX inhibitors, IL-12, or IFNγ but was inhibited by MK886 (a leukotriene synthesis inhibitor), anti-TNFα, anti-CXCL1, and anti-CXCL5 antibodies and by repertaxin (a CXCR1/2 antagonist). These treatments all inhibited mBSA- or IL-23-induced neutrophil migration. IL-17 induced neutrophil chemotaxis through a CXC chemokines-dependent pathway. Our results suggest that prostaglandin plays an important role in IL-23-induced neutrophil migration in arthritis by enhancing IL-17 synthesis and by inhibiting IL-12 and IFNγ production. We thus provide a mechanism for the pathogenic role of the IL-23/IL-17 axis in RA and also suggest an additional mechanism of action for nonsteroidal anti-inflammatory drugs.

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Neutrophils are thought to play an important role in the tissue damage observed in various autoimmune diseases. Chemokines, cytokines and leukotrienes have recognized roles in the orchestration of neutrophil migration. We have recently shown that antigeninduced neutrophil migration into the peritoneum of immunized mice is mediated by macrophage-inflammatory protein (MIP)-1a which interacts with CCR1 and induces the sequential release of TNF-a and leukotriene B 4 (LTB 4 ). The present study investigates the role of MIP-2 and CXCR2 in the cascade of events leading to mediator generation and neutrophil influx. Antigen challenge of immunized mice induced the expression of CXCR2 and the production of KC and MIP-2 proteins. Antigen-induced neutrophil migration was inhibited by a CXCR2 receptor antagonist (repertaxin) or an anti-MIP-2 antibody, but not by an anti-KC antibody. Administration of MIP-2 promoted a dose-dependent neutrophil migration in naive mice which was inhibited by repertaxin, anti-TNF-a, anti-MIP-1a antibodies or by MK886 (leukotriene synthesis inhibitor). MIP-2 administration induced the release of MIP-1a, TNF-a and LTB 4 , and the release of the latter two was inhibited by anti-MIP-1a antibody treatment. Our studies highlight the intricate balance between mediator production and action during an immune-mediated inflammatory response and suggest a mediator cascade leading to neutrophil influx following antigen challenge of immunized mice: MIP-2 ? MIP-1a ? TNF-a ? LTB 4 .

Liver transplantation has become a standard treatment for end-stage liver disease and the number of recipients has grown rapidly in the last few years. Dental care during pre-transplant workup is important to reduce potential sources of infection in the drug-induced immunosuppression phase of liver transplantation.Objectives The objectives of this study were to document the prevalence of oral abnormalities in patients on a liver transplant waiting list presenting to an urban dental school clinic, discuss the appropriate dental treatment according their systemic conditions and compare their oral manifestations with those of healthy individuals. Material and Methods A pilot study was conducted involving 16 end-stage liver disease individuals (study group- SG) attending the Special Care Dentistry Center of the University of São Paulo and 16 control individuals (control group- CG) with no liver diseases, receiving dental care at the Dental School of the University of São Paulo. These individuals were assessed for their dental status (presence of oral disease or abnormalities), coagulation status, and dental treatment indications. Results The patients from SG exhibited a greater incidence of oral manifestations compared with CG (p=0.0327) and were diagnosed with at least one oral disease or condition that required treatment. Coagulation abnormalities reflecting an increased risk of bleeding were found in 93.75% of the patients. However, no bleeding complications occurred after dental treatment. Conclusions The patients with chronic liver diseases evaluated in this study exhibited a higher incidence of oral manifestations compared with the control group and had at least one oral disease or abnormality which required dental treatment prior to liver transplantation. Careful oral examination and evaluation of the patient, including laboratory tests, will ensure correct oral preparation and control of oral disease prior to liver transplantation.

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Nodular fasciitis is a lesion found in the subcutaneous fascia that micoscopically presents as a benign proliferation of fibroblasts and myofibroblasts, which may be mistaken for a sarcoma due to clinically rapid growth. Diagnosis is by histopathology and of the immunohistochemical profile. We describe a case of nodular fasciitis in the oral cavity that demonstrated partial spontaneous regression. The patient was a 32-year-old man with a buccal mucosal mass, which had grown rapidly for 45 days. On microscopic examination, the lesion displayed a well-delineated but not encapsulated proliferation of spindle cells, with a nodular growth pattern. Immunohistochemical analysis showed positivity of the spindle cells for the antibodies against smooth muscle actin and muscle-specific actin (HHF-35). Treatment of such lesions typically involves complete conservative excision, but the lesion may regress eventually in the absence of definitive treatment.