Protective major histocompatibility complex genes and the role of interleukin‐4 in collagen‐induced arthritis

Hesse, Matthias; Bayrak, S; Mitchison, Avrion

doi:10.1002/eji.1830261259

Cited by 29 publications

(21 citation statements)

References 21 publications

(12 reference statements)

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“…This issue regarding IL-4, namely a Th2 cytokine acting similarly to IL-13, seems to conflict with our data, and it is difficult to generalize these data rationally. Hesse reported that treatment with an IL-4-neutralizing antibody over a period extending over 6 days post immunization exacerbated the collagen-induced arthri- tis, but when curtailed to 2 days post immunization, the disease was reduced [24]. Anti-IL-4 antibody therapy may act in a complicated way in the course of an autoimmune disease.…”

Section: Discussion Effect Of Il-13-ig Gene Transfer On Eammentioning

confidence: 99%

The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism

et al. 2005

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Interleukin (IL)-13 is a pleiotropic cytokine secreted by activated Th2 T lymphocytes. Th1 cytokines are assumed to exacerbate and Th2 cytokines to ameliorate rat experimental autoimmune myocarditis (EAM). Here, we examined the effect of IL-13 on EAM, using a hydrodynamics-based delivery of an IL-13-Ig fusion gene, as well as the possible mechanism of its effect. Rats were immunized on day 0, and IL-13-Ig-treated rats were injected with pCAGGS-IL-13-Ig, and control rats with pCAGGS-Ig, on day 1 or 7. On day 17, the IL-13-Ig gene therapy was effective in controlling EAM as monitored by a decreased heart weight/body weight ratio, by reduced myocarditis and by reduced atrial natriuretic peptide mRNA in the heart, as a heart failure marker. On the basis of IL-13 receptor mRNA expression in separated cells from EAM hearts, we proposed that IL-13-Ig target cells were CD11b + cells and non-cardiomyocytic noninflammatory (NCNI) cells, such as fibroblasts, smooth muscle or endothelial cells. IL-13-Ig inhibited expression of the genes for prostaglandin E synthase, cyclooxygenase-2, inducible nitric oxide synthase, IL-1b and TNF-a in cultivated cells from EAM hearts, while it enhanced expression of the IL-1 receptor antagonist gene. We conclude that IL-13-Ig ameliorates EAM and suppose that its effectiveness may be due to the influence on these immunologic molecules in CD11b + and NCNI cells.

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Section: Discussion Effect Of Il-13-ig Gene Transfer On Eammentioning

confidence: 99%

The effect of hydrodynamics-based delivery of an IL-13-Ig fusion gene for experimental autoimmune myocarditis in rats and its possible mechanism

et al. 2005

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“…Its H2E molecule is no longer expressed, as commonly occurs in mice (36,37). The promoter at its H2Ab locus gives its H2A molecule some of functions of the missing H2E, namely high expression (23,38), and a consequent effect on Th1͞Th2 balance that affects disease susceptibility (39,40). The wild-derived inbred strains that have this type of promoter at H2Ab are CZECH, LEWES, MOR, PERC, SK, SF, TIRANO, WSB, ZALENDE, and M. caroli.…”

Section: Discussionmentioning

confidence: 99%

Patterned variation in murine MHC promoters

Mitchison¹,

Roes²

2002

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

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To compare variation in regulatory and coding DNA, promoter sequences have been obtained from wild-derived mice and laboratory rats. The sequences are from the proximal promoter of the H2Aa, H2Ab, H2Eb, and H2K genes of 24 wild-derived inbred strains and a sample of the corresponding exon 2 sequences and of the RT1.Ba gene of six strains of laboratory rat. They reveal a high level of variation in the mouse MHC class II promoters (H2A and H2E), a low level in MHC class I (H2K), and none in the rat. The variation is pronounced in and around the cAMP response element, a major binding site for modulating promoter activity in response to external stimulation. This finding, together with the different levels of variation in MHC classes I and II, is suggestive of natural selection. However, selection operating via the MHC coding sequences must also contribute, as indicated by the minimal variation in both the MHC class II promoter and coding sequences of the rat. Furthermore CIITA (trans-activator of class II) of the mouse has been reported to have minimal variation in its promoter and none in its coding sequence. Taken together these data suggest that the regulatory and coding sequences undergo coselection. Each of the mouse class II promoters has a pattern of variation that appears to be basically dimorphic, with further variation added by recombination͞mutation. The dimorphic allelic lineages are in marginally detectable linkage disequilibrium with the exon 2 sequences, particularly in H2Aa, thus lending further support to the coevolution hypothesis.

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“…Crosses with naturally C5-deficient mice indicate that an intact C5 gene is required for the disease to develop (10). Furthermore, substitution in the MHC of a class II allele that suppresses the early burst of IL-4 production partially protects against the disease, in accordance with the need for this early burst as demonstrated by treatment of mice with anti-IL-4 monoclonal antibody (11,12).…”

mentioning

confidence: 83%