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IL-4 mRNA Expression (il-4 + mrna_expression)
Selected AbstractsThe human basophil , a novel target of the neuropeptide alpha-melanocyte-stimulating hormoneEXPERIMENTAL DERMATOLOGY, Issue 8 2006M. Böhm There is increasing evidence that the basophil does not only play an important role in acute allergic reactions but also in the pathogenesis of chronic allergic disorders. Here we show that human basophils express melanocortin receptors (MC-Rs) and respond to alpha-melanocyte-stimulating hormone (alpha-MSH) with regulation of proallergic cytokine expression and modulation of basophil activation markers. Using primers against all known MC-R subtypes we demonstrate that the human basophil cell line KU812 expresses MC-1R. Expression of MC-1R on the surface of KU812 cells was confirmed by FACS analysis using an anti-MC-1R antibody. The MC-1R expressed by KU812 cells was functionally active as alpha-MSH induced intracellular cAMP in a dose-dependent manner. Moreover, alpha-MSH abrogated the effect of calcium ionophore A23187 on IL-4 mRNA expression in these cells. The relevance of the above findings was corroborated by showing that MC-1R surface expression is also detectable in basophils of leukocyte suspensions derived from whole human blood. Most interestingly, alpha-MSH was capable of suppressing the inductive effect of fMLP on surface expression of the basophil activation marker CD63 in leukocyte suspensions of atopic individuals. Likewise, alpha-MSH significantly blocked grass pollen-induced up-regulation of CD63 in leukocyte suspensions of patients with grass pollen allergy. Our findings highlight a novel functional dimension of alpha-MSH. In addition, MSH peptides may become a novel future therapeutic avenue in treating human allergic diseases. [source] Inflammatory cytokines modulate chemokine production patterns of HepG2 cells toward initially inclined directionHEPATOLOGY RESEARCH, Issue 5 2009Tomohiko Ohashi Aim:, Human hepatocytes are known to express an array of inflammatory cytokines and chemokines. In this study, we examined the potential roles of hepatocytes in regulating immune responses in the liver, by assessing the induction of Th1- or Th2-specific chemokines in HepG2 cells after various inflammatory stimulations. Methods:, HepG2 cells were stimulated with IL-1,, IFN-,, IL-4, IL-10, and/or CCL2, harvested at several time points, and served for the analyses of cytokine/chemokine mRNA expressions by semi-quantitative RT-PCR. Results:, (i) IL-1, up-regulated mRNA levels of CXCL8, CXCL10, and CCL2. IFN-, increased those of CXCL9, CXCL10, and CCL5, while IL-4 or IL-10 had no effect. (ii) Addition of IL-4 to the culture of IFN-,-stimulated cells, down-regulated CXCL9 and CXCL10 mRNA levels. (iii) Addition of IFN-, to the culture of IL-1,-stimulated cells, further up-regulated CXCL9 and CXCL10 mRNA levels. Addition of IL-4 decreased CXCL8 and CXCL10 levels, and increased CCL2 level in IL-1,-stimulated cells. (iv) CCL2 induced IL-4 mRNA expression. Conclusions:, IFN-, augmented mRNA expression of Th1-specific chemokines (CXCL9 and CXCL10) in HepG2 cells. IL-4 had no effect on those of Th2-spesific chemokines (CCL17 and CCL22); however, it was supposed to augment Th2 response indirectly through the induction of CCL2 under the inflammatory condition. The findings suggest that hepatocytes have ability to promote immune responses in the liver toward the direction, initially determined by the cytokine balances in the local inflammatory region. [source] Interleukin-16 inhibits interleukin-13 production by allergen-stimulated blood mononuclear cellsIMMUNOLOGY, Issue 1 2006Souad El Bassam Summary Expression of interleukin (IL)-16 is increased in bronchial mucosal biopsies of atopic asthmatics compared to normal controls. The functional significance of increased expression of IL-16 at sites of allergic inflammation is not yet clear. We have previously shown that IL-16 inhibits IL-5 secretion by allergen-stimulated peripheral blood mononuclear cells (PBMC). We investigated whether IL-16 inhibits the production of other T helper 2 cytokines, namely IL-13 and IL-4, by allergen-specific T cells. PBMC from ragweed-sensitive atopic subjects were stimulated with allergen extract for cytokine production in the presence or absence of rhIL-16. Production of cytokines was assessed by enzyme-linked immunosorbent assay and reverse transcription,polymerase chain reaction. To evaluate whether the modulatory effect of IL-16 on cytokine synthesis was mediated by interferon-, (IFN-,), IL-10, IL-12 or IL-18, allergen-stimulated PBMC were cultured in presence of IL-16 and neutralizing concentrations of relevant antibodies. Allergen-stimulated PBMC produced significantly elevated levels of IL-13 (90,740 pg/ml) as compared to unstimulated PBMC (0,375 pg/ml, P < 0·01). Addition of rhIL-16 resulted in down-regulation of IL-13 mRNA expression as well as significantly reduced amounts of IL-13 released by allergen-stimulated PBMC (0,457 pg/ml, P < 0·001), as observed for IL-5. No effect of IL-16 was observed on IL-4 mRNA expression. Treatment with IL-16 resulted in increased levels of IL-10 and IL-18 in allergen-stimulated cell culture. Neutralization of IFN-,, IL-12, IL-10 or IL-18 did not alter the inhibitory effects of IL-16 on IL-13 and IL-5 secretion by allergen-stimulated PBMC. IL-16 did not modify IL-13 synthesis by anti-CD3-stimulated CD4+ T cells, but it significantly reduced the production of IL-5. These data suggest that IL-16 may play an important immunoregulatory role in allergic states in response to allergen. [source] Th2 polarization of the immune response of BALB/c mice to Ixodes ricinus instars, importance of several antigens in activation of specific Th2 subpopulationsPARASITE IMMUNOLOGY, Issue 2 2001Naceur Mejri BALB/c mice were infested with Ixodes ricinus larvae, nymphs or adults. Expression of IL-4 and IFN-, mRNA in axillary and brachial draining lymph node cells were measured by competitive quantitative reverse transcription-polymerase chain reaction 9 days after the beginning of primary-infestation. IL-4 mRNA was always higher than that of IFN-, mRNA for all tick instars. Moreover, IL-4 mRNA expression progressively increased during nymphal primary-infestation with a high burst of expression 7 days after the beginning of infestation. No evolution of IFN-, mRNA expression was detected. Draining lymph node cells of infested BALB/c produced higher level of IL-4 than IFN-, following in vitro restimulation with adult tick saliva, salivary gland extract (SGE) or with five selected different chromatographic fractions of SGE. Anti-tick IgG1 antibodies but no IgG2a were detected in BALB/c pluri-infested with I. ricinus nymphs, which confirmed the Th2 polarization of the immune response. [source] UVB Irradiation of Normal Human Skin Favors the Development of Type-2 T-cells In Vivo and in Primary Dermal Cell Cultures,PHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 3 2002Sergio Di Nuzzo ABSTRACT To determine the effect of UVB exposure on the balance of type-1 or type-2 T-cells in skin, we examined the expression of key markers interferon (IFN)-, and interleukin (IL)-4 in cryostat sections. IFN-, mRNA was clearly detectable in nonirradiated control skin, and IFN-, protein was found in 2% of the dermal CD3pos T-cells, whereas IL-4 mRNA was hardly detectable, and no IL-4 protein was found. In contrast, IL-4 mRNA expression increased upon irradiation, and IL-4 was found in 2% of the T-cells at day 2 after UVB-exposure. Concomitantly, IFN-, mRNA expression decreased, and IFN-, protein became absent. We also analyzed T-cells present in primary dermal cell cultures, which were used as an in vitro equivalent of the in vivo situation. As compared with T-cells from control skin, T-cells in dermal cell cultures from UVB-exposed skin displayed an increased IL-4 and decreased IFN-, expression. No such skewing occurred when the T-cells from irradiated skin were cloned in the absence of a dermal microenvironment. Except for an occasional positive T-cell, type-1,associated cell-surface markers (CCR5, CXCR3) or type-2 markers (CCR3, CD30, CRTH2) were undetectable in situ. But these markers were expressed on cultured dermal T-cells from UVB-exposed and control skin at a comparable level, but did not correlate with the IFN-, and IL-4 production. Altogether, UVB-induced changes of the dermal microenvironment favor the development of type-2 T-cells. [source] | ||||||||||