Cytokine profiles of skin lesions in murine lupus models

Nishide, Takeshi; Yoshimasu, Takashi; Ikeda, Takaharu; Seo, Naohiro; Ohtani, Toshio; Furukawa, Fukumi

doi:10.1016/j.descs.2005.06.005

Cited by 5 publications

(7 citation statements)

References 33 publications

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“…The expression of H2R on lymphocytes was not observed in the skin lesions of MRL/l. The expressions of IL-12 and TNF-were common in the skin lesions of drug-induced DLE model and MRL/l mice, while the expression patterns of IFN-and IL-10 differs in these mice [9]. The difference of cytokine productions in these lupus models might depend on the location of HRs expression.…”

Section: Discussionmentioning

confidence: 94%

“…The expression of H2R was present in significant levels in the skin of 2-month-old MRL/l mice and H2R expression was continued and then decreased within skin lesions at 5 months of age as determined by RT-PCR. Previously, we detected significant expression of IL-2, IL-10, IL-12 and TNFmRNAs in skin lesions from 5-month-old MRL/l mice, compared with non-lesional skin from 2-month-old MRL/l mice [9]. It is possible that the accumulation of mast cells (CD117 (+)) expressing H2R occurs to suppress the productions of Th1 and Th2 cytokine expressed in the skin lesions of MRL/l mice.…”

Section: Discussionmentioning

confidence: 99%

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The Expression of Histamine Receptors in Skin Lesions of MRL/MPlpr/ lpr Mice

Yoshimasu¹,

Kanazawa²,

Mikita³

et al. 2008

TODJ

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Systemic lupus erythematosus (SLE) is a chronic inflammatory disease accompanied with systemic organs disorder including skin changes. The MRL/MP-lpr/lpr (MRL/l) mouse is a model of human LE. MRL/l mice skin lesions exhibit a decreased activity in histamine-N-methyltransferase (HMT) and impaired histamine metabolism. In order to clarify the role of histamine receptors (HRs) including H1R, H2R and H3R in MRL/l skin lesions, the relationship between HRs and skin lesions was assessed by immunohistochemical staining and RT-PCR methods. The expression of H2R was seen in the non-lesional skin of 2-month-old (mo) MRL/l mice; H2R expression continued for a couple of months, and then decreased in the skin lesions of 5-mo MRL/l mice. In MRL/l skin lesions, a dense mast cell infiltration expressed H2R was seen. In conclusion, an increased expression of H2R in mast cells may be associated with histamine metabolism in skin lesions from MRL/l mice.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The Expression of Histamine Receptors in Skin Lesions of MRL/MPlpr/ lpr Mice

Yoshimasu¹,

Kanazawa²,

Mikita³

et al. 2008

TODJ

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“…The silencing of dsDNAspecific B cells, resulting in decreased cell numbers that enter into the plasma cell pool [11] and the simultaneous partial elimination of already present plasma cells by low doses of the Bz, successfully delay the development of this aggressive autoimmune disease. The severe cutaneous inflammatory lesions and lymphadenopathy in the studied Fas-deficient mouse strain are known to be due to a massive accumulation of T cells [16][17][18][19][20][21]. The chimeric antibody and Bz target B lineage cells; however, Bz is also known to reduce double-negative, double-positive and CD4…”

Section: Discussionmentioning

confidence: 99%

Targeted silencing of DNA-specific B cells combined with partial plasma cell depletion displays additive effects on delaying disease onset in lupus-prone mice

Nikolova-Ganeva

Gesheva

Todorov

et al. 2013

Clinical and Experimental Immunology

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SummaryTargeting autoreactive B lymphocytes at any stage of their differentiation could yield viable therapeutic strategies for treating autoimmunity. All currently used drugs, including the most recently introduced biological agents, lack target specificity. Selective silencing of double-stranded DNA-specific B cells in animals with spontaneous lupus has been achieved previously by the administration of a chimeric antibody molecule that cross-links their DNAreactive B cell immunoglobulin receptors with inhibitory FcγIIb (CD32) receptors. However, long-lived plasmacytes are resistant to this chimeric antibody as well as to all conventional treatments. Bortezomib (a proteasome inhibitor) depletes most plasma cells and has been shown recently to suppress disease activity in lupus mice. We hypothesized that the co-administration of non-toxic doses of bortezomib, that partially purge long-lived plasma cells, together with an agent that selectively silences DNAspecific B cells, should have additive effects in an autoantibody-mediated disease. Indeed, our data show that the simultaneous treatment of lupusprone MRL/lpr mice with suboptimal doses of bortezomib plus the chimeric antibody resulted in the prevention or the delayed appearance of the disease manifestations as well as in a prolonged survival. The effect of the combination therapy was significantly stronger than that of the respective monotherapies and was comparable to that observed after cyclophosphamide administration.

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“…Increased levels of IFN-c mRNA expression are detected in LE-like skin lesions of experimentallyinduced knockout mice, along with increased tumor necrosis factor-a (TNF-a) and IL-12 levels, but not in MRL ⁄ lpr mice. 49,50 CXCR3, which the majority of infiltrating cells in human CLE lesions express, is found predominantly on the surface of IFN-c-producing Th1 cells. 51 CXCL10 and CXCL9 are upregulated in CLE lesions by IFN-a stimulation, and those chemokines belong to the Th1 type family of chemokines.…”

Section: Ifn-cmentioning

confidence: 99%

Recent advances in cytokines in cutaneous and systemic lupus erythematosus

Mikita¹,

Ikeda²,

Ishiguro³

et al. 2011

The Journal of Dermatology

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Lupus erythematosus (LE) includes a broad spectrum of diseases from a cutaneous-limited type to a systemic type. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease which affects multiple organs. Cutaneous lupus erythematosus (CLE) includes skin symptoms seen in SLE and cutaneous-limited LE. Although immune abnormalities, as well as heritable, hormonal and environmental factors, are involved in the pathology of LE, the actual pathogenesis is still unclear. Recently, the involvement of various cytokines has been shown in the pathogenesis of LE. Moreover, some trials with biological agents targeted specific cytokines are also ongoing for SLE. In this article, we review the contributions of major cytokines such as interferon, tumor necrosis factor-α and interleukin-18 to LE, especially SLE and CLE.

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Cytokine profiles of skin lesions in murine lupus models

Cited by 5 publications

References 33 publications

The Expression of Histamine Receptors in Skin Lesions of MRL/MPlpr/ lpr Mice

The Expression of Histamine Receptors in Skin Lesions of MRL/MPlpr/ lpr Mice

Targeted silencing of DNA-specific B cells combined with partial plasma cell depletion displays additive effects on delaying disease onset in lupus-prone mice

Recent advances in cytokines in cutaneous and systemic lupus erythematosus

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