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Abstract Fanconi anemia is a rare autosomal recessive disease. In this disease, cytokine pathways can induce the bone marrow failure that is observed in individuals with Fanconi anemia. Interleukin IL-17 exhibits a protective effect in organisms because it induces neutrophil recruitment and shows a pathological role in several models of autoimmune diseases, periodontal disease, cancer, allograft rejection, and graft versus host disease. Polymorphisms in the IL17A and IL17RA genes were evaluated from DNA in saliva, comparing individuals with or without Fanconi anemia, using models of genotypic transmission (additive, dominant, and recessive). Polymorphisms in the IL17A and IL17RA genes (rs2241044 [C allele], rs879577 [C allele], rs9606615 [T allele], and rs2241043 [C allele]) were risk factors for developing Fanconi anemia. We also performed an analysis of gene markers with clinical variables in the Fanconi group. Polymorphisms in the IL17A gene (rs3819025 [A allele] and rs2275913 [G allele], respectively) were associated with an age of less than 20 years (p = 0.026; RP 0.65) and the female sex (p = 0.043; RP 0.88). The IL17RA gene was also associated with age and the presence of leukoplakia (a potentially malignant oral disorder). An age of less than 20 years was associated with rs917864 (T allele; p = 0.036; RP 0.67). The presence of leukoplakia was associated with rs17606615 (T allele; p = 0.042; RP 0.47). To our knowledge, this is the first study that associates IL17A and IL17RA gene polymorphisms with Fanconi anemia and examines rs2241044 polymorphisms in scientific literature thus far.
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Background:There is no specific therapy for inflammatory bowel disease(IBD),and the pathogenesis of IBD is not fully clear. Aims:To explore the expression and clinical significance of IL-17BR in colon mucosa and peripheral blood mononuclear cell(PBMC)of patients with IBD. Methods:Colon mucosal biopsy specimens of 40 Crohn's disease(CD) patients,32 ulcerative colitis(UC)patients and 25 healthy controls and PBMC of 30 CD patients,27 UC patients and 25 healthy controls were collected. The expressions of IL-17BR in colon mucosa and PBMC were determined by immunohistochemistry and flow cytometry,respectively,and correlations between IL-17BR expression and levels of CRP, ESR,CDAI score and Mayo score were analyzed. Serum levels of TNF-α before and after infliximab(IFX)treatment were determined by ELISA,and correlations with IL-17BR were analyzed. Results:Compared with healthy controls,IL-17BR expressions in colon mucosa of CD and UC patients were significantly increased(P<0.05). IL-17BR expressions were significantly higher in active CD and UC patients than in remission CD and UC patients(P <0.05). No significant differences in IL-17BR expression in PBMC were found among CD,UC patients and healthy controls(P>0.05). The expression of IL-17BR in colon mucosa was positively correlated with CRP,ESR,CDAI score or Mayo score in CD,UC patients(P <0.05). After treatment with IFX,expression of IL-17BR in colon mucosa and serum TNF-α level were significantly decreased in CD patients(P<0.01). Expression of IL-17BR was positively correlated with serum TNF-α level in CD patients(P<0.05). Conclusions:The increasing of IL-17BR expression in IBD patients is closely correlated with activity of inflammation and TNF-α level. IL-17BR may play a vital role in immune response of intestinal mucosa,and can be used as a new marker for reflecting the activity of IBD.
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Interleukin (IL)17 is a pro-inflammatory cytokine produced by the activated CD4 + T cell subsets (Th17).It can regulate the function of cells involving in the pathogenesis of inflammation,autoimmune,neoplastic disease.The IL-17 family consists of six family members,IL-17A,IL-17B,IL-17C,IL-17D,IL-17E and IL-17F,respectively.The IL-17 receptor family consists of five members,IL-17RA,IL-17RB,IL-17RC,IL-17RD and IL-17RE,respectively.This review summarizes the characteristics and functions of the IL-17 family,the IL-17 receptor family,and the Th17/IL-17 axis.It also reviews the research about IL-17 in various kidney diseases.
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Objective To investigate the correlation of plasma interleukin ( IL)-17 level and IL-17 receptor (IL-17R) expression in the thymus of patients with myasthenia gravis (MG).Methods The blood samples of 63 patients (38 with glucocorticoid treatment, 25 with thymus removal) who admitted to Henan Provincial People′s Hospital between 2010 and 2014 were collected at three different stages: pre-treatment, 1 week post-treatment and 1 month post-treatment.The blood samples of 42 healthy controls were also collected.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-17 in plasma.Twenty-five thymus tissues from MG patients and another 12 thymus tissues from patients with congenital heart disease who had surgery therapy were also collected.Reverse transcription polymerase chain reaction was used to evaluate the mRNA levels of IL-17R.The possible correlation between the expression of IL-17 and IL-17R with MG was analyzed.Results Before treatment, the levels of IL-17 in the plasma were much higher in all the MG patients ( both ocular and generalized) when compared to the healthy controls ( controls (3.2 ±0.7) pg/ml, MG patients (8.5 ±1.7) pg/ml, t =2.450, P 0.05, compared to the healthy controls).In the surgery therapy cases, the IL-17 levels were also reduced after the thymus removal ( pre-surgery (8.8 ±1.4) pg/ml, 1 week after surgery (5.3 ±0.7) pg/ml, t=1.950, P<0.05;1 month after surgery (3.0 ±0.4) pg/ml, t=2.683, P<0.01).In the thymus tissues of the MG patients, the mRNA levels of IL-17R were much higher than that of the controls ( relative level 2.31 folds, t =2.682, P <0.01).Meanwhile, a positive correlation was found between the plasma IL-17 levels and the relative IL-17R levels in thymus tissues ( r =0.945 4, P <0.01 ).Furthermore, IL-17 was positively correlated with quantitative myasthenia gravis scores (QMGS) either pre-treatment (r =0.798 1, P <0.01) or post-treatment (r=0.906 5, P<0.01).And IL-17R was positively correlated with QMGS pre-treatment (r=0.775 5, P<0.01).Conclusions IL-17 is increased in the plasma of MG patients (both ocular and generalized) , and is decreased upon the glucocorticoid treatment or surgery therapy, suggesting that it can be used as a parameter to determine the therapeutic effects.IL-17R is increased in the thymus tissues of MG patients, suggesting that it can potentially be used as a pathological diagnosis parameter.
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ObjectiveToinvestigatetheroleofimmuneinflammatoryreactionintheformationof intracranial aneurysm. Methods The intracranial aneurysms in 40 patients of craniotomy ( intracranial aneurysm group) and the vascular specimens in 20 craniotomy patients w ith traumatic brain injury (control group) w ere col ected. Fluorescence quantitative polymerase chain reaction w as used to detect the expression of interleukin (IL)-17 receptor in the arterial w al . Flow cytometry w as used to detect the Th-17 cel s in peripheral blood. Enzyme-linked immunosorbent assay w as used to measure the levels of IL-17, IL-6 in the arterial w al and tumor necrosis factor-α( TNF-α) in peripheral blood. Results There w ere no significant differences in the age (62.6 ±8.7 years vs.61.4 ±7.9 years;t=0.342;P=0.681), proportions of male (60.0%vs.65.0%; χ2 =0.246, P=0.434), hypertension ( 12.5%vs.10.0%; χ2 =0.315, P=0.492), diabetes (75.0%vs.10.0%; χ2 =0.284, P=0.482), and smoking (35.5%vs.30.0%; χ2 =0.224, P=0.413) betw een the intracranial aneurysms group and the control group. The expression of IL -17 receptor in the arterial w al (0.106 ±0.032 vs.0.264 ±0.071; t=5.115, P=0.001) and the proportion of Th17 cels in peripheral blood (2.75%±0.53%vs.7.18%±1.54%; t=8.436, P<0.001) and IL-17 level ( 7.32 ±1.82 μg/L vs.22.64 ±4.51 μg/L; t= 8.357, P< 0.001 ) in the control group w ere significantly low er than those in the intracranial aneurysm group. The levels of IL-6 (1.15 ±0.24 μg/L vs. 19.64 ±4.16 μg/L; t=9.527, P<0.001) and TNF-α(1.43 ±0.31 μg/L vs.26.17 ±4.32 μg/L; t=9.816, P<0.001) in the arterial wal in the control group were significantly lower than those in the intracranial aneurysm group. Conclusions The expression of IL-17 receptor in the arterial w al , the proportion of the Th17 cels and IL-17 level in peripheral blood were increased in patients with intracranial aneurysms. Immune inflammation may be involved in the formation of intracranial aneurysm.
ABSTRACT
Th17 cells (Th17) are a distinct lineage of CD4+ T cells that secrete high amounts of IL-17 under orphan nuclear receptor retinoic acid receptor-related orphan receptor gammat (RORgammat) which is a lineage-specific transcription factor. TGF-beta and inflammatory cytokines, such as IL-6, IL-21, IL-1beta, and IL-23, play central roles in the generation of Th17 cells. Th17 cells and their effector molecules, such as IL-17A, IL-17F, IL-21, IL-22, and CCL20, contribute to the progression and pathogenesis of several autoimmune and inflammatory diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease and systemic lupus erythematosus. Studies of Th17 development and the effects of IL-17 signaling in autoimmune responses suggest a high potential for targeting this pathway in immune pathologies. In this review, we discuss Th17 biology in relation to autoinflammatory disorders and the various therapeutic strategies under investigation which target the IL-17-Th17 cell pathway in chronic inflammatory autoimmune disorders.