Associação do polimorfismo de IL-13 (+1398A/G) com a asma e a ancestralidade genômica / Association of IL-13 (+1398A/G) gene polymorphisms with asthma and genomic ancestry

Introdução: A asma é uma doença complexa, resultante da interação entre fatores genéticos e ambientais. A expressão aumentada de genes relacionados à inflamação define as alterações celulares e estruturais do aparelho respiratório, enquanto o meio ambiente modula os diferentes fenótipos asmáticos. Os produtos dessas células envolvidos na inflamação incluem citocinas, como a interleucina13 (IL-13), que está relacionada com a síntese direta de IgE, imunoglobulina essencial na patogênese da asma. Há divergências entre a prevalência da asma e o grupo étnico estudado, desta forma, o uso de Marcadores Informativos de Ancestralidade (AIM ­ Ancestry Informative Markers) possibilita a caracterização da ancestralidade genômica de diferentes populações. Objetivos: Verificar a associação entre polimorfismos do gene IL-13R com a ancestralidade genômica e a asma em uma população no sul da Bahia. Métodos: Foram genotipadas 320 amostras, sendo 114 casos, e 206 controles, utilizando o método de PCR e PCR/RFLP em sete AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM e PV92) que apresentam elevado diferencial de frequência alélica entre africanos, ameríndios e europeu, e um polimorfismo no receptor de IL-13 (IL-13RA1). Resultados: Os resultados desse estudo mostraram que a maior contribuição foi ameríndia, tanto para os casos (37,42%), como para os controles (50,52%), demonstrando que há diferenças nas contribuições étnicas das amostras da região estudada. O polimorfismo no receptor de IL-13 (IL- 13RA1) apresentou associação significativa com rinite e história familiar. Conclusões: A heterogeneidade da composição étnica das amostras pode ter influenciado na não associação das duas variáveis: níveis de IgE sérico e histórico familiar, e a presença do polimorfismo no receptor da IL-13RA1, e aponta a necessidade de realização do controle genômico.

Introduction: Asthma is a complex disease resulting from the interaction between genetic and environmental factors. Increased expression of inflammatory genes defines cellular and structural changes in the respiratory tract, while the environment modulates the different asthmatic phenotypes. Cell products involved in inflammation include cytokines, such as interleukin-13 (IL-13), which is related to the direct synthesis of IgE, an immunoglobulin that plays a key role in the pathogenesis of asthma. Because there is divergence of asthma prevalence between different ethnic groups, the use of ancestry informative markers (AIMs) allows for the characterization of genomic ancestry in different populations. Objectives: To examine the association of IL-13R gene polymorphisms with genomic ancestry and asthma in a population from the south of Bahia. Methods: A total of 320 samples, 114 cases and 206 controls, were genotyped using PCR and PCR/RFLP methods for 7 AIMs (Sb19.3, APO, AT3, RB2300, LPL, CKMM, and PV92) that showed a high allele frequency differential between Africans, Amerindians, and Europeans and 1 polymorphism in the IL-13 receptor (IL-13RA1). Results: Amerindian ancestry provided the greatest contribution in both cases (37.42%) and controls (50.52%), indicating that there are differences in the ethnic contribution of the samples from the study region. The IL-13 receptor (IL-13RA1) polymorphism was significantly associated with rhinitis and family history. Conclusions: Heterogeneity in the ethnic composition of the samples may have influenced the non-association of serum IgE levels and family history with the presence of IL-13RA1 receptor polymorphism, and the results point to the need for genomic control.

The impact of interleukin-13 receptor expressions in cell migration of astrocytomas / O impacto da expressão dos receptores de interleucina-13 na migração celular em astrocitomas

INTRODUCTION: Astrocytomas are common brain tumors. Increased expression levels of Interleukin-13 Receptor α2 (IL-13RA2) have been reported in astrocytomas. The Interleukin-13 signaling pathway may be associated with cell migration when binding to Interleukin-13 Receptor α1. OBJECTIVE: To investigate Interleukin-13 Receptor α1 (IL-13RA1) and IL13RA2 expression levels in human diffusely infiltrative astrocytomas and test the involvement of Interleukin-13 levels in cell migration in two glioblastoma cell lines. METHODS: IL13RA expression levels were accessed by quantitative real time PCR in 128 samples of astrocytomas and 18 samples of non-neoplastic brain tissues from temporal lobe epilepsy surgery. The impact of IL-13 levels (10 and 20 ng/mL) on cell migration was analyzed by the wound assay in U87MG and A172 cells. RESULTS: Glioblastoma presented higher IL13RA1 and IL13RA2 expression levels compared to lower grades astrocytomas and to non-neoplastic cases. U87MG and A172 cells presented higher expression levels of IL-13RA1 vs. IL-13RA2. A significant difference in migration rate was observed in A172 cells treated with 10 ng/mL of IL-13 vs. control: treated cells presented slower migration than non-treated cells. U87MG cells treated with IL-13 20ng/mL presented slower migration than non-treated cells. This indicates that the IL13Rα1 signaling pathway was not activated, indeed inhibited by the decoy IL-13Rα2, slowing cell migration. This impact occurred with a lesser concentration of IL-13 on the A172 than on the U87MG cell line, because A172 cells have a higher IL-13RA2/A1 ratio. CONCLUSION: The present results suggest IL-13 receptors as possible targets to decrease tumor cell migration.

INTRODUÇÃO Astrocitomas são os tumores cerebrais mais frequentes. Nestes tumores foi observada maior expressão do receptor de Interleucina-13 α2 (IL13RA2). A cascata de sinalização da Interleucina-13 pode estar associada com a migração celular, após sua ligação com o receptor de Interleucina-13 α1 (IL13Rα1). OBJETIVO: Investigar os níveis de expressão dos receptores de Interleucina-13 (IL13RA1 e IL13RA2) em astrocitomas difusamente infiltrativos e avaliar o envolvimento da Interleucina-13 na migração celular de duas linhagens de glioblastoma. MÉTODOS: A expressão dos receptores IL13RA foi analisada por PCR em tempo real, em 128 amostras de astrocitomas e 18 amostras de tecido cerebral não neoplásico, provenientes de cirurgia de epilepsia do lobo temporal. E o impacto da quantidade de IL-13 (10ng/ml e 20ng/ml) em ensaio de migração celular. RESULTADOS: As amostras de Glioblastoma apresentaram maior expressão de IL13RA1 and IL13RA2 comparados com astrocitomas de baixo grau e os casos não-neoplásicos. Nas células U87MG e A172 foi observado maior nível de expressão de IL-13RA1 do que IL-13RA2. Uma diferença significativa na taxa de migração foi obtida em células A172 tratadas com 10 ng/mL comparadas com o controle: as células tratadas apresentaram menor migração que as células não tratadas. As células U87MG tratadas com 20ng/mL de IL-13 apresentaram menor migração celular que as células não tratadas. A diferença na migração celular indica que o caminho de sinalização de IL13Rα1 não foi ativado e foi inibido pelo IL-13Rα2, diminuindo a migração celular. Esse impacto ocorreu com uma concentração menor de IL-13 nas células A172 ao contrário da U87MG, porque as células A172 possuem uma razão IL-13RA2/A1 maior. CONCLUSÃO: os resultados sugerem que os receptores de IL-13 podem ser utilizados como possíveis alvos para a diminuição da migração celular tumoral.

Effect of combined use of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of sIL-5Rα and sIL-13Rα2 on VCAM-1 and IFN-γ in allergic rhinitis rats.</p><p><b>METHODS</b>A total of 50 Wistar rats were randomly divided into 5 groups: the normal group (group A), the allergic rhinitis model group (group B), the sIL-5Rα treatment group (group C), the sIL-13Rα2 treatment group (group D), the combination of sIL-5Rα and sIL-13Rα2 treatment group (group E or the combined treatment group). Rats in the latter 4 groups were sensitized with ovalbumin (OVA) and Al(OH)(3), and challenged with OVA to establish allergic rhinitis models, while rats in the normal group were treated with saline. Rats in the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group were absorbed on day 31 to day 38 once daily once nasal cavity with sIL-5Rα(100 µg), sIL-13Rα2 (100 µg) and the combination of sIL-5Rα (100 µg) and sIL-13Rα2 (100 µg) 30 min before challenged, while rats in the allergic rhinitis model group received PBS(50 µl). Then the levels of VCAM-1 and IFN-γ in serum and nasal lavage fluid (NLF) were measured by ELISA.</p><p><b>RESULTS</b>Compared with the normal group, the levels of VCAM-1 in the allergic rhinitis model group were higher, while IFN-γ were lower (all P < 0.01). Compared with the allergic rhinitis model group, the sIL-5Rα treatment group, the sIL-13Rα2 treatment group and the combined treatment group could effectively reduced serum and NLF VCAM-1 level [group E: (283.5 ± 5.7) µg/L, (101.8 ± 4.8) µg/L; group C: (311.5 ± 12.6) µg/L, (133.9 ± 5.8) µg/L; group D: (304.7 ± 6.6) µg/L, (128.5 ± 7.7) µg/L], and increased IFN-γ level [group E: (874.7 ± 9.6) pg/ml, (349.2 ± 12.1) pg/ml; group C: (600.2 ± 16.1) pg/ml, (195.5 ± 16.1) pg/ml; group D: (577.9 ± 9.6) pg/ml, (196.7 ± 9.9) pg/ml ]; compared with single treatment, the combined treatment group also had significant differences(P < 0.01).</p><p><b>CONCLUSIONS</b>Combined treatment with sIL-5Rα and sIL-13Rα2 to treat the allergic rhinitis rats can significantly reduce VCAM-1 levels in serum and NLF, and increase IFN-γ levels, thus, to achieve the purpose of mitigation and treatment of allergic rhinitis.</p>

Effects of interleukin 13 on the differentiation and expression of transcription factor c-fos of HEL cells / 中华血液学杂志

<p><b>OBJECTIVE</b>To study the effects of IL-13 on the differentiation and expression of transcription factor c-fos of human erythroleukemia cell line (HEL) cells.</p><p><b>METHODS</b>Reverse transcription polymerase chain reaction (RT-PCR) was used to observe the mRNA expression of IL-13 receptor a 1, GP i b, vWF and c-fos, and Western blot and cytometry were used to analyse their protein expression.</p><p><b>RESULTS</b>IL-13 receptor a 1 was expressed on HEL cells. IL-13 (100 ng/ml ) up-regulated the mRNA expression of GP II b and vWF. The ratio of luminous absorption (LA) of GP I b to p-actin bands ( AB) was 1. 303 in control group, whereas was 2. 912 in experiment group; being 2. 23-fold higher than that in control group (P < 0. 05). The ratio of LA to AB for vWF was 0.217 in control group, and 0. 506 in experiment group; indicating a 2. 33-fold increase in experiment group (P <0. 05). The protein expression of GP I b and vWF was significantly increased in experiment group, compared with that in control group. IL-13 inducing the increased expression of c-fos mRNA and protein of HEL cells peaked at 30 min and 60 min, respectively. The ratio of LA to AB for c-fos was also increased at 30 min and 60 min (P <0. 05).</p><p><b>CONCLUSION</b>IL-13 prompts the differentiation of HEL cells and up-regulates the expression of c-fos.</p>

IL-4/IL-13 Cytokine and Receptor in Asthma / 소아알레르기및호흡기학회지

Asthma is a chronic allergic inflammatory disease of lung. The initiation and progression of asthma is dependent on the cytokines interleukin (IL) -4 and IL-13 acting through related receptor complexes. Disease pathogenesis is effected by intracellular signaling pathways that couple primarily to specific motifs within the intracellular domain of the IL-4 receptor alpha chain (IL-4R alpha), a subunit that is common to the IL-4 and IL-13 receptor complexes. Neutralizing anti-cytokine strategies have proven to be highly successful on dissecting relevant effector pathways in experimental allergic disease, and are now entering clinical trials in human allergic disorders. Although there have been only a few clinical studies on the effects of cytokine modulators in asthma, this line of research and development appears promising.

Involvement of interleukin-13 and soluble Inter leukin-2 receptors in the clinico-pathological presentation of pediatric nephrotic syndrome

54 children with nephrotic syndrome and 17 healthy controls were included in the study, among cases studied 40 were males and 14 were females, 36 had history of hypertension and 12 cases had oedema at the time of sampling. Patients were divided into 4 groups, GP 1:10 cases were. steroid responsive in remission, GP 11:12 cases were steroid resistant during activity, GP III:18 cases were steroid dependent of low dose steroids and GP IV:14 cases were steroid dependent on high dose steroids. For all patients' full history, clinical examination and estimation of urinary proteins as well as serum level of IL-13 and sIL-R11 were done. The level of serum JL-13 was significantly lower in cases, compared to control, interquartile range [IQR] was II and 28 respectively [p<0.005] Comparison of the 4 groups revealed a highly significant correlation between groups II and I [p<0.0054]. groups II and IV [p<0.010], there was also a significant difference in serum IL-I 3 level in both sexes but no significant relation to presence of oedema or hypertension. There was a significant negative correlation between IL-13 and serum protein level [r =-0.2686, p<0.05]. On the other hand the serum level of slL-2R was significantly higher in children with NS compared to controls [1Q11=5000, 1244 respectively, p<0.005]. There was a significant difference between patients in GPI vs OP IV [p<0.0 126] and between OP II vs OP Ill [p<0.029] and a highly significant difference between OP II vs OP IV [p<0.0012]. There was no significant difference as regards sex, but a significant difference in children with oedema [p<0.0090] and a highly significant difference in those with hypertension [p<0.0015]. There was also a significant negative correlation between sIL-2R and steroid intake [r =-0.49, 2 0.03]. Results of renal biopsy had no significant correlation with either IL-13 or sIL-2R. In conclusion TL-13 was significantly lower in all studied groups compared to the control, indicating involvement of IL-13 in the pathogenesis of NS. SIL-2R is involved in pathogenic mechanisms involved in activation of NS so it can be used as a clue for disease activity. The exact role of inflammatory cytolcines in pathogenesis of NS in childhood needs further research work to reach proper understanding of the pathogenesis of this syndrome