Physiologic Regulation of Postovulatory Neutrophil Migration into Vagina in Mice by a C-X-C Chemokine(s)

Sonoda, Yuri; Mukaida, Naofumi; Wang, Jianbin; Shimada-Hiratsuka, Motoko; Naito, Makoto; Kimura, Tadashi; Harada, Akihisa; Inoue, Masakí; Matsushima, Kouji

doi:10.4049/jimmunol.160.12.6159

Cited by 74 publications

(1 citation statement)

References 27 publications

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“…We were interested in exploring the vagina-specific neuroimmune interface using a novel ex vivo mouse model. The mouse vagina, similar to the human vagina, is highly innervated 30 , comprised of stratified squamous epithelial cells 31 , and contains an abundance of immune cells [32][33][34][35] . In the present study, we aimed to investigate the characteristics of the neuroimmune interface in the mouse vagina.…”

Section: Introductionmentioning

confidence: 99%

Time course of lipopolysaccharide- and capsaicin-induced cytokine release in an ex vivo mouse model of vaginal inflammation

Chalmers

Hutchinson

Dodds

et al. 2023

Preprint

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Problem: The neuroimmune interface has been characterised in few areas of the body. The objective of this study was to investigate the neuroimmune interface in the mouse vagina through a novel ex vivo model, to determine whether LPS could directly activate and produce TRPV1-mediated neuronal activation. Method of Study: Concentrations of IL-1β and IL-6 release into the supernatant at different times post ex vivo stimulation with LPS, capsaicin, or a combination of the two were assessed using enzyme-linked immunosorbent assay. Results: There were no differences in the supernatant concentration of IL-6 with different stimulation type nor stimulation time. Supernatant concentrations of IL-1β were greater at the 20 hour time point than the 4 hour time point, and were greater for stimulations involving LPS. Conclusion: There is a clear pattern of pro-inflammatory neuroimmune responses following ex vivo stimulation of mouse vaginal tissues with capsaicin and LPS, evident as an increased IL-1β output. This output is greatest at 20 hours post-stimulation, indicating this neuroimmune response is time-dependent.

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Section: Introductionmentioning

confidence: 99%

Time course of lipopolysaccharide- and capsaicin-induced cytokine release in an ex vivo mouse model of vaginal inflammation

Chalmers

Hutchinson

Dodds

et al. 2023

Preprint

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Ablation of the Ccr2 gene exacerbates polyarthritis in interleukin‐1 receptor antagonist–deficient mice

Fujii¹,

Baba²,

Ishida³

et al. 2010

Arthritis & Rheumatism

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Objective. The pathogenesis of rheumatoid arthritis (RA) involves cytokines and chemokines. Given the role of intraarticular macrophage infiltration in RA, this study was undertaken to address the pathogenic role of CCR2, a chemokine receptor that is abundantly expressed by macrophages, in Il1rn-deficient mice, a mouse model of RA.Methods. Il1rn-deficient and Il1rn and Ccr2-double-deficient mice were subjected to clinical assessment of arthritis and histologic examination. Bone mineral density was measured with computed tomography. The types of cells infiltrating joints were determined by immunohistochemical analysis and flow cytometric analysis. Osteoclasts in joints were quantified after tartrate-resistant acid phosphatase staining. Cytokine and chemokine levels were measured by enzymelinked immunosorbent assay and multiplex suspension array assay. The expression patterns of chemokines and osteoclastogenic factors were determined by doublecolor immunofluorescence analysis. Anti-mouse CXCR2 antibody was injected into Il1rn and Ccr2-doubledeficient mice for blocking experiments.Results. Ablation of the Ccr2 gene actually exacerbated arthritis and intraarticular osteoclastogenesis, while it enhanced intraarticular neutrophil but not macrophage accumulation in Il1rn-deficient mice. Infiltrated neutrophils expressed the osteoclastogenic factors RANKL and ADAM-8, thereby augmenting intraarticular osteoclastogenesis in Il1rn and Ccr2-doubledeficient mice. Moreover, the double-deficient mice exhibited enhanced expression of the neutrophilic chemokines keratinocyte chemoattractant and macrophage inflammatory protein 2 (MIP-2), compared with Il1rn-deficient mice. Finally, neutralizing antibodies to CXCR2, the receptor for keratinocyte chemoattractant and MIP-2, dramatically attenuated arthritis in Il1rn and Ccr2-double-deficient mice.Conclusion. Our findings indicate that CCR2-mediated signals can modulate arthritis in Il1rn-deficient mice by negatively regulating neutrophil infiltration.

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Opposite roles of neutrophils and macrophages in the pathogenesis of acetaminophen‐induced acute liver injury

et al. 2006

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Neutrophils and macrophages infiltrate after acetaminophen (APAP)-induced liver injury starts to develop. However, their precise roles still remain elusive. In untreated and control IgG-treated wild-type (WT) mice, intraperitoneal APAP administration (750 mg/kg) caused liver injury including centrilobular hepatic necrosis and infiltration of neutrophils and macrophages, with about 50% mortality within 48 h after the injection. APAP injection markedly augmented intrahepatic gene expression of inducible nitric oxide synthase (iNOS) and heme oxygenase (HO)-1. Moreover, neutrophils expressed iNOS, which is presumed to be an aggravating molecule for APAP-induced liver injury, while HO-1 was mainly expressed by macrophages. All antigranulocyte antibody-treated neutropenic WT and most CXC chemokine receptor 2 (CXCR2)-deficient mice survived the same dose of APAP, with reduced neutrophil infiltration and iNOS expression, indicating the pathogenic roles of neutrophils in APAPinduced liver injury. However, APAP caused more exaggerated liver injury in CXCR2-deficient mice with reduced macrophage infiltration and HO-1 gene expression, compared with neutropenic WT mice. An HO-1 inhibitor, tin-protoporphyrin-IX, significantly increased APAP-induced mortality, implicating HO-1 as a protective molecule for APAP-induced liver injury. Thus, CXCR2 may regulate the infiltration of both iNOS-expressing neutrophils and HO-1-expressing macrophages, and the balance between these two molecules may determine the outcome of APAP-induced liver injury. IntroductionAcetaminophen (APAP) is widely prescribed as an analgesic and antipyretic drug in clinics and is also sold as numerous over-counter preparations as a single compound or in combination with other medications [1, 2]. Although it is generally safe, an overdose of APAP can cause severe liver failure with a significant morbidity and mortality. Thus, its wide availability and severe toxicities has placed APAP overdose as the leading cause for calls to Poison Control Centers in the United States (>100 000/year). Moreover, APAP overdose accounts for more than 56 000 emergency room visits, 2600 hospitalizations, and an estimated 458 deaths due to acute liver failure each year in the United States alone [3]. The toxic response is initiated by the metabolism of APAP to a toxic metabolite, N-acetyl-p-benzoquinone imine. Because N-acetyl-p-benzoquinone imine can react rapidly with sulfhydryl groups, it first depletes glutathione in hepatocytes and then reacts with a number of intracellular proteins, thereby causing their dysfuntions [4, 5]. APAP-induced liver injury is histopathologically characterized by centrilobular hepatic necrosis with a massive infiltration of leukocytes, particularly neutrophils. The recruitment of leukocytes in the damaged tissue is a hallmark of the inflammatory process, which may contribute to the development of APAP-induced liver injury [6,7]. In line with this assumption, accumulating evidence has implicated neutrophils as the leukocyte type essentially involved i...

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Physiologic Regulation of Postovulatory Neutrophil Migration into Vagina in Mice by a C-X-C Chemokine(s)

Cited by 74 publications

References 27 publications

Time course of lipopolysaccharide- and capsaicin-induced cytokine release in an ex vivo mouse model of vaginal inflammation

Time course of lipopolysaccharide- and capsaicin-induced cytokine release in an ex vivo mouse model of vaginal inflammation

Ablation of the Ccr2 gene exacerbates polyarthritis in interleukin‐1 receptor antagonist–deficient mice

Opposite roles of neutrophils and macrophages in the pathogenesis of acetaminophen‐induced acute liver injury

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