Objective: Allergic airway diseases (AADs) are a group of heterogeneous disease mediated by T-helper type 2 (Th2) immune response and characterized with airway inflammation and remodeling, including allergic asthma, allergic rhinitis, and chronic rhinosinusitis with allergic background. This review aimed to discuss the abnormal epithelial-mesenchymal crosstalk in the pathogenesis of AADs. Data Sources: Articles referred in this review were collected from the database of PubMed published in English up to January 2018. Study Selection: We had done a literature search using the following terms "allergic airway disease OR asthma OR allergic rhinitis OR chronic sinusitis AND IL-25 OR IL-33 OR thymic stromal lymphopoietin OR fibrocyte". Related original or review articles were included and carefully analyzed. Results: It is now believed that abnormal epithelial-mesenchymal crosstalk underlies the pathogenesis of AADs. However, the key regulatory factors and molecular events involved in this process still remain unclear. Epithelium-derived triple cytokines, including interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP), are shown to act on various target cells and promote the Th2 immune response. Circulating fibrocyte is an important mesenchymal cell that can mediate tissue remodeling. We previously found that IL-25-circulating fibrocyte axis was significantly upregulated in patients with asthma, which may greatly contribute to asthmatic airway inflammation and remodeling. Conclusions In view of the redundancy of cytokines and "united airway" theory, we propose a new concept that IL-25/IL-33/TSLP-fibrocyte axis may play a vital role in the abnormal epithelial-mesenchymal crosstalk in some endotypes of AADs. This novel idea will guide potential new intervention schema for the common treatment of AADs sharing common pathogenesis in the future.
Asthma ; metabolism ; physiopathology ; Cytokines ; physiology ; Humans ; Interleukin-17 ; physiology ; Interleukin-33 ; physiology

OBJECTIVETo detect the expression and distribution of interleukin-17 and interleukin 17 receptor (IL-17R) in nasal polyps and to probe into their significance in the pathology of nasal polyps.

METHODSThe methods of immunohistochemical staining and western blot were used to detect IL-17 and IL-17R in nasal polyps and controls.

RESULTSIn nasal polyp tissues, IL-17 expressed mainly in cytoplasm of plasm cell, less in prickle-cell layer of the epithelium and the acinus of the serous gland. In turbinates, IL-17 also expressed in the cytoplasm of the plasm cell, the prickle-cell layer of the epithelium and the acinus of the serous gland. The expression of IL-17 between nasal polyps and turbinates differed significantly (t = 2.237, 2.176, 2.246, P < 0.05, respectively). Both IL-17 and IL-17R displayed specific bands in nasal polyps and turbinates, but the bands of IL-17 and IL-17R in nasal polyps were stronger than those in turbinates.

CONCLUSIONSIL-17 may have an important role in the occurrence of nasal polyps by specific combination with IL-17R and over-expression in nasal polyps.

Adult ; Aged ; Case-Control Studies ; Female ; Humans ; Interleukin-17 ; metabolism ; Male ; Middle Aged ; Nasal Polyps ; metabolism ; pathology ; Receptors, Interleukin-17 ; metabolism

OBJECTIVE: To explore the effect of cytokine levels on early death and coagulation function of patients with newly diagnosed acute promyelocytic leukemia (APL). METHODS: Routine examination was performed on 69 newly diagnosed APL patients at admission. Meanwhile, 4 ml fasting venous blood was extracted from the patients. And then the supernatant was taken after centrifugation. The concentrations of cytokines, lactate dehydrogenase (LDH) and ferritin were detected by using the corresponding kits. RESULTS: It was confirmed that cerebral hemorrhage was a major cause of early death in APL patients. Elevated LDH, decreased platelets (PLT) count and prolonged prothrombin time (PT) were high risk factors for early death (P <0.05). The increases of IL-5, IL-6, IL-10, IL-12p70 and IL-17A were closely related to the early death of newly diagnosed APL patients, and the increases of IL-5 and IL-17A also induced coagulation disorder in APL patients by prolonging PT (P <0.05). In newly diagnosed APL patients, ferritin and LDH showed a positive effect on the expression of IL-5, IL-10 and IL-17A, especially ferritin had a highly positive correlation with IL-5 (r =0.867) and IL-17A (r =0.841). Moreover, there was a certain correlation between these five high-risk cytokines, among which IL-5 and IL-17A (r =0.827), IL-6 and IL-10 (r =0.823) were highly positively correlated. CONCLUSION Elevated cytokine levels in newly diagnosed APL patients increase the risk of early bleeding and death. In addition to the interaction between cytokines themselves, ferritin and LDH positively affect the expression of cytokines, thus affecting the prognosis of APL patients.
Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Cytokines/metabolism* ; Interleukin-10 ; Interleukin-17/metabolism* ; Interleukin-6/metabolism* ; Interleukin-5/metabolism* ; Blood Coagulation Disorders ; Ferritins ; Tretinoin

OBJECTIVETo investigate the expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura (ITP) and its significance.

METHODSThe quantity of CD4(+)CD25(+)T cells, CD4(+)CD25(high) T cells and CD4(+) IL-17(+)T cells in peripheral blood were measured with flow cytometry (FCM), the plasma level of IL-10 and IL-17 with ELISA and the expression of Foxp3 mRNA and RORc mRNA with RT-PCR in 29 newly diagnosed ITP patients and 28 healthy controls.

RESULTSThe ratio of CD4(+)CD25(+)T cells/CD4(+) T cells in the peripheral blood of ITP patients was significantly higher than that of the normal controls (P < 0.05). And the ratio of CD4(+)CD25(high) T/CD4(+) T cells in the patients was remarkably lower (P < 0.05). There was no difference in the percentage of CD4(+) IL-17(+)T/CD4(+) T cells between ITP patients and controls (P > 0.05). The ratio of Treg/Th17 was lower in ITP patients (P < 0.05). The plasma level of IL-10 in ITP patients was significantly decreased (P < 0.05), whereas no statistical difference was observed in the level of IL-17 (P > 0.05). The Foxp3 mRNA expression levels were largely reduced (P < 0.05), but the RORc mRNA expression was increased compared with that in controls (P < 0.05).

CONCLUSIONThe imbalance of Treg/Th17 plays an important role in the pathogenesis of ITP.

Humans ; Interleukin-10 ; metabolism ; Interleukin-17 ; Purpura, Thrombocytopenic, Idiopathic ; blood ; T-Lymphocytes, Regulatory ; metabolism ; Th17 Cells ; metabolism

OBJECTIVES: To investigate the expression of IL-25,IL-33 and EOS in children with allergic rhinitis (AR). METHODS: Ninety-four AR children receiving immunotherapy and 23 healthy people were concluded in the study. The serum levels of IL-25 and IL-33 were detected by Enzyme-linked Immunosorbent Assay (ELISA), and a count of EOS were measured. RESULTS: The serum levels of IL-25 and IL-33 in the mild group were higher than control group (<0.05). The count of EOS showed no difference between the mild group and the control group (>0.05). The serum levels of IL-25 and IL-33 in the severe group were higher than those in mild group (<0.05). The serum levels of IL-25 and IL-33 in the severe group were higher than control group (<0.05). The count of EOS in the severe group were higher than those in mild group (<0.05). The count of EOS in the severe group were higher than those in control group (<0.05). Spearman test showed the serum levels of IL-25 in the children with AR patients have positive correlation with the serum levels of IL-33 (<0.05, =0.238). CONCLUSIONS Expression of IL-25 levels, IL-33 levels and the count of EOS in patients with AR are enhanced, which shows that IL-25, IL-33 and the count of EOS are involved in the AR. If we can understand the mechanism of them, it will profound implications for treatment.
Child ; Enzyme-Linked Immunosorbent Assay ; Eosinophils ; Humans ; Immunotherapy ; Interleukin-17 ; metabolism ; Interleukin-33 ; metabolism ; Rhinitis, Allergic ; immunology ; therapy

OBJECTIVETo investigate the role of CCL20/CCR6/Th17 axis in vascular invasion and metastasis of primary hepatocellular carcinoma (HCC).

METHODSExpression levels of CCL20 mRNA in the normal human liver cell line L-02, and human hepatocellular carcinoma cell lines Hep3B, Huh7 and HepG2 were quantified by using SYBR green real time PCR. CCL20 secretions from these cell lines were quantified by using ELISA. The chemotactic effect of HCC cell line Hep3B on human peripheral blood mononuclear cells was determined by using transwell chemotaxis assay. Pre-therapy serum levels of IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-17, IL-23, IFN-γ, TNF-α and CCL20 in 93 patients with HCC were measured by using 9-plex array and ELISA. All the patients were chronic hepatitis B virus associated HCC, and 51 cases were those with vascular invasion and metastasis (metastasis group) and 42 cases were not (non-metastasis group). CCL20 and CCR6 mRNA expressions in the HCC and tumor-adjacent tissues were determined by using SYBR Green real time PCR in 41 patients, among them, 20 cases were from the group of patients with metastasis and 21 cases were from the group of patients without metastasis. The CCL20 expression was further determined by immunohistochemistry.

RESULTSThe HCC cell lines expressed and secreted higher amount of CCL20, which effectively recruited CCR6(+) T cells. Pre-therapy serum levels of CCL20 in 93 HCC patients were (38.2 ± 28.4)pg/ml, significantly increased than those with benign hepatic hemangiomas [(7.8 ± 17.8)pg/ml, P < 0.01]. In addition, the serum levels of CCL20 were positively correlated with the tumor diameters in HCC patients (r = 0.32, P = 0.0018). CCL20 was dominantly expressed in the cytoplasm in HCC cells, and it was also expressed by some infiltrating immune cells. The mRNA expression levels of CCL20 of the tumor tissues were significantly higher than that in the tumor-adjacent tissues (P < 0.05). Multivariate logistic regression analysis showed that serum levels of IL-17 and CCL20 were independent risk factors of metastasis in HCC patients (P < 0.05 for both). CCL20 mRNA showed no statistically significant differences between patients with metastasis and without metastasis in both tumor tissues and tumor-adjacent tissues (P > 0.05 for both). But the patients with metastasis showed significantly higher expressions of CCR6 both in their tumor [5.75 (1.79, 19.13)]and tumor-adjacent tissues [7.99 (4.49, 19.54)] than those with non-metastasis [1.69 (0.76, 2.87) and 3.58 (1.84, 4.32), P < 0.05 for both].

CONCLUSIONCCL20/CCR6/Th17 axis may promote vascular invasion and metastasis hepatocellular carcinoma.

Bile Duct Neoplasms ; Carcinoma, Hepatocellular ; metabolism ; Chemokine CCL20 ; metabolism ; Humans ; Interleukin-10 ; metabolism ; Interleukin-17 ; metabolism ; Interleukin-23 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Leukocytes, Mononuclear ; Liver Neoplasms ; metabolism ; RNA, Messenger ; Th17 Cells ; Tumor Necrosis Factor-alpha ; metabolism

BACKGROUND: As a potent pro-inflammatory cytokine of the interleukin (IL)-1 family, IL-18 was elevated in early active and progressive plaque-type psoriatic lesions and that serum or plasma levels of IL-18 correlated with the Psoriasis Area and Severity Index (PASI). Although results from previous studies have established that IL-18 may aggravate psoriatic inflammation, the mechanisms of this process remain unknown. In this study, IL-18 knock out (KO) mice and wild-type (WT) mice were used to investigate the effects of IL-18 within a mouse model of psoriasis. METHODS: WT and IL-18 KO mice were divided into four groups, including imiquimod (IMQ)-treated IL-18 KO group (n = 11) and WT group (n = 13) as well as their respectively gene-matched control mice (receiving vaseline; n = 12). PASI scores were used to evaluate psoriatic lesions in IMQ-treated mice. Pathological features and dermal cellular infiltration were investigated by hematoxylin and eosin staining. The levels of psoriasis-related cytokines including IL-23, IL-17, IL-12, IL-1β, IFNγ, IL-15, IL-27, and IL-4 were tested by real-time polymerase chain reaction (PCR). The protein level of IL-1β, IL-27, CXCL1, and Ly6 g were investigated by immunohistochemistry (IHC). RESULTS: Acanthosis (98.46 ± 14.12 vs. 222.68 ± 71.10 μm, P < 0.01) and dermal cell infiltration (572.25 ± 47.45 vs. 762.47 ± 59.59 cells/field, P < 0.01) were significantly milder in IMQ-induced IL-18 KO mice compared with that in WT mice. IMQ-induced IL-18 KO mice manifested larger areas of Munro microabscesses (11,467.83 ± 5112.09 vs. 4093.19 ± 2591.88 μm, P < 0.01) and scales (100,935.24 ± 41,167.77 vs. 41,604.41 ± 14,184.10 μm, P < 0.01) as compared with WT mice. In skin lesions of IL-18 KO mice, the expressions of IL-1β, IL-4, and IL-27 were all significantly upregulated but IL-17 was decreased. Histologically, strong positive signals of Ly6g were observed within the epidermis of IL-18 KO mice but expressions of CXCL1 were decreased. CONCLUSIONS IL-18 may exacerbate prominent inflammation and influence pathological features in IMQ-induced mouse model of psoriasis. IL-18 may upregulate pro-inflammatory cytokines and reduce protective cytokines, thus aggravating psoriatic inflammation. In addition, IL-18 may be involved in the formation of Munro microabscesses and scales.
Animals ; Chemokine CXCL1 ; metabolism ; Cytokines ; metabolism ; Disease Models, Animal ; Imiquimod ; toxicity ; Interleukin-17 ; metabolism ; Interleukin-18 ; metabolism ; Mice ; Mice, Knockout ; Psoriasis ; chemically induced ; genetics ; metabolism ; Skin ; immunology ; metabolism

BACKGROUNDVulvovaginal candidiasis is caused by Candida albicans. The vaginal epithelium, as the first site of the initial stage of infection by pathogens, plays an important role in resisting genital tract infections. Moreover, lactobacilli are predominant members of the vaginal microbiota that help to maintain a normal vaginal microenvironment. Therefore, Lactobacillus crispatus was explored for its capacity to intervene in the immune response of vaginal epithelial cells VK2/E6E7 to C. albicans.

METHODSWe examined the interleukin-2 (IL-2), 4, 6, 8, and 17 produced by VK2/E6E7 cells infected with C. albicans and treated with L. crispatus in vitro. The capacity of L. crispatus to adhere to VK2/E6E7 and inhibit C. albicans growth was also tested by scanning electron microscopy (SEM) and adhesion experiments.

RESULTSCompared with group VK2/E6E7 with C. albicans, when treated with L. crispatus, the adhesion of C. albicans to VK2/E6E7 cells decreased significantly by 52.87 ± 1.22%, 47.03 ± 1.35%, and 42.20 ± 1.55% under competition, exclusion, and displacement conditions, respectively. SEM revealed that the invasion of C. albicans into VK2/E6E7 cells was caused by induced endocytosis and active penetration. L. crispatus could effectively protect the cells from the virulence of hyphae and spores of C. albicans and enhance the local immune function of the VK2/E6E7 cells. The concentrations of IL-2, 6, and 17 were upregulated significantly (P < 0.01) and that of IL-8 were downregulated significantly (P < 0.01) in infected VK2/E6E7 cells treated with L. crispatus. The concentration of IL-4 was similar to that of the group VK2/E6E7 with C. albicans (24.10 ± 0.97 vs. 23.12 ± 0.76 pg/ml, P = 0.221).

CONCLUSIONSL. crispatus can attenuate the virulence of C. albicans, modulate the secretion of cytokines and chemokines, and enhance the immune response of VK2/E6E7 cells in vitro. The vaginal mucosa has a potential function in the local immune responses against pathogens that can be promoted by L. crispatus.

Candida albicans ; pathogenicity ; Cell Line, Tumor ; Epithelial Cells ; immunology ; metabolism ; microbiology ; ultrastructure ; Female ; Humans ; Interleukin-17 ; metabolism ; Interleukin-2 ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-6 ; metabolism ; Interleukin-8 ; metabolism ; Lactobacillus crispatus ; physiology ; Microscopy, Electron, Scanning ; Vagina ; cytology

OBJECTIVE: To investigate the effect of IL-17 and IL-23 in the pathogenesis of allergic rhinitis(AR) and non. allergic rhinitis(NAR). METHOD: Selected 156 cases of patients with allergic rhinitis (AR group) and 59 cases of patients with non-allergic rhinitis (NAR group), 60 cases of healthy people (control group). All cases in AR group and NAR groups were evaluated by a visual analog scale (VAS) score of nasal symptoms. Collected peripheral blood and nasal secretions in all cases and then detected IL-17 and IL-23 expression levels. RESULT: There was no significant difference in VAS score of AR group and NAR group (P>0. 05). IL-17 and IL-23 levels of serum and nasal secretions in AR group and NAR group were both higher than control group, with a highly significant difference (P <0. 05). The research showed a clear correlation between expression of IL-17 and IL-23 both in serum and nasal secretions of AR group and NAR(P<0. 05). CONCLUSION IL-17 and IL-23 may be important cytokines and IL-23/IL-17 pathway may play a significant role in the pathogenesis of allergic rhinitis and non-allergic rhinitis.
Case-Control Studies ; Humans ; Interleukin-17 ; blood ; metabolism ; Interleukin-23 ; blood ; metabolism ; Nasal Mucosa ; metabolism ; Rhinitis ; blood ; metabolism ; Rhinitis, Allergic ; blood ; metabolism

OBJECTIVE: To investigate the role of IL-17A in promoting the activation of lung fibroblasts and the secretion of chemokine CXCL12, and to explore the possible mechanism. METHODS: Lung tissues of BALB/c mice were collected after intraperitoneal injection of recombinant mouse IL-17A (rmIL-17A). Real-time RT-PCR and Western blotting were used to detect the expression levels of α-smooth muscle actin (α-SMA) and collagen I in lung tissues, and immunohistochemical staining and real-time RT-PCR were used to determine the expression of CXCL12. Normal mouse primary lung fibroblasts were isolated and cultured, and identified by immunofluorescence staining with optical microscopy. Cells and supernatant of culture medium were collected after stimulation with rmIL-17A at different concentrations. mRNA levels of α-SMA, collagen I, and CXCL12 in the cells were determined by real-time RT-PCR, and the levels of collagen I and CXCL12 in the supernatant of culture medium were determined by ELISA. RESULTS: The mRNA and protein levels of α-SMA and collagen I in the lung tissue of mice injected with rmIL-17A were significantly increased compared with the control group (all CONCLUSIONS s: IL-17A can promote the activation of lung fibroblasts and translation into myofibroblast. The secretion of collagen is increased, which promote the deposition of extracullular matrix, and leads to the occurrence and development of lung fibrosis. CXCL12, a chemokine secreted by activated fibroblasts, may be involved in this process.
Actins/genetics* ; Animals ; Cells, Cultured ; Chemokine CXCL12/metabolism* ; Fibroblasts/metabolism* ; Interleukin-17/pharmacology* ; Lung/metabolism* ; Mice ; Mice, Inbred BALB C