BACKGROUND: Psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes. OBJECTIVE: The purpose is to understand the pathogenetic mechanisms of psoriasis by comparing immunoreactivity of various chemokines and chemokine receptors between lesional and non-lesional skin of psoriasis. METHODS:We have performed immunohistochemical studies with mouse anti-human IL-8, mouse anti-human GRO, anti-huamn MCP-1, mouse anti-human RANTES, anti-human CDw 128 IL-8RA/ CXCR1, and anti-human IL-8RB/CXCR2 for lesional and non-lesional skin of ten psoriatic patients. RESULTS: 1.Immunohistochemical reactivity for IL-8 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for GRO-alpha is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 2.Immunohistochemical reactivity for MCP-1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05), and immunohistochemical reactivity for RANTES is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 3.Immunohistochemical reactivity for CXCR1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for CXCR2 is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 4.Immunofluorescent staining reveals positive finding in epidermis of lesional psoriasis, but negative finding in CXCR2. CONCLUSION: These results suggest that psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and that both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes.
Animals ; Chemokine CCL5 ; Chemokines* ; Chemokines, CC ; Chemokines, CXC ; Epidermis ; Humans ; Interleukin-8 ; Keratinocytes ; Mice ; Psoriasis* ; Receptors, Chemokine* ; Receptors, Interleukin-8B ; Skin

BACKGROUND: Psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes. OBJECTIVE: The purpose is to understand the pathogenetic mechanisms of psoriasis by comparing immunoreactivity of various chemokines and chemokine receptors between lesional and non-lesional skin of psoriasis. METHODS:We have performed immunohistochemical studies with mouse anti-human IL-8, mouse anti-human GRO, anti-huamn MCP-1, mouse anti-human RANTES, anti-human CDw 128 IL-8RA/ CXCR1, and anti-human IL-8RB/CXCR2 for lesional and non-lesional skin of ten psoriatic patients. RESULTS: 1.Immunohistochemical reactivity for IL-8 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for GRO-alpha is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 2.Immunohistochemical reactivity for MCP-1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05), and immunohistochemical reactivity for RANTES is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 3.Immunohistochemical reactivity for CXCR1 is stronger in lesional epidermis than non-lesional epidermis(p<0.05) and immunohistochemical reactivity for CXCR2 is stronger in lesional epidermis than non-lesional epidermis(p<0.05). 4.Immunofluorescent staining reveals positive finding in epidermis of lesional psoriasis, but negative finding in CXCR2. CONCLUSION: These results suggest that psoriatic keratinocytes express CXC chemokines like IL-8 and GRO-alpha, and CC chemokines like MCP-1 and RANTES, which have a significant role in the accumulation of inflammatory cells in psoriatic skin and that both CXCR1 and CXCR2 receptors are also expressed in psoriatic keratinocytes, which suggests that IL-8 and GRO-alpha could have a role in the characteristic epidermal changes through binding to their receptors in psoriatic keratinocytes.
Animals ; Chemokine CCL5 ; Chemokines* ; Chemokines, CC ; Chemokines, CXC ; Epidermis ; Humans ; Interleukin-8 ; Keratinocytes ; Mice ; Psoriasis* ; Receptors, Chemokine* ; Receptors, Interleukin-8B ; Skin

Interleukin-8 (IL-8), which is a member of C-X-C chemokine subfamily, is an important activator and chemoattractant for neutrophils and has been implicated in a variety of inflammatory diseases. Numerous reports show that various cells express IL-8 mRNA and produce IL-8 protein rapidly, including monocytes, T lymphocytes, neutrophils, fibroblasts, endothelial cells and epithelial cells. The human IL-8 gene has a length of 5191 bp and contains four exons separated by three introns. It maps to human chromosome 4q12-q21. The mRNA consists of a 101 bases 5' untranslated region, an open reading frame of 297 bases, and a long 3' untranslated region of 1.2 kb. The 5' flanking region of the IL-8 gene contains potential binding sites for several nuclear factors including activated protein-1 (AP-1), activated protein-2 (AP-2), nuclear factor-gene binding (NF-kappa B), nuclear factor-interleukin-6 (NF-IL-6, also calls CAAT/enhancer-binding proteins, C/EBP), IFN regulatory factor-1 (IRF-1), hepatocyte nuclear factor-1 (HNF-1), and so on. IL-8 gene expression is regulated initially at the level of gene transcription. The rapid induction of IL-8 gene expression is likely mediated by latent transcription factors that bind the IL-8 promoter. AP-1 and NF-IL-6 physically interact with NF-kappa B, and functional cooperativity among these factors appears to be critical for optimal IL-8 promoter activity in different cell types. The IL-8 receptor (IL-8R) is a dimeric glycoprotein consisting of a 59 KDa and a 67 KDa subunit. It has been given the name CDw128. It is expressed in many different cell types including those not responding to IL-8. The receptor density is approximately 20,000/cell in neutrophils, 1,040/cell in monocytes, and 300/cell in T-lymphocytes. The IL-8R is a member of the family of G-protein-coupled receptors. There are at least two different IL-8 receptor types (CXCR1 and CXCR2). The activities of IL-8 are not species-specific. IL-8 affects the adhesion of neutrophils to the endothelium and induces the transendothelial migration of neutrophils. IL-8 also exhibits in vitro chemotactic activities against of T-lymphocytes and basophils. IL-8 gene expression can be regulated by fluid shear stress, which may play an important role in the genesis and development of both inflammation and arterosclerosis.
Gene Expression Regulation ; Interleukin-8 ; chemistry ; genetics ; physiology ; Receptors, Interleukin

OBJECTIVE: Schizophrenia is a disabling disorder of unknown aetiology, lacking definite diagnostic method and cure. A reliable biological marker of schizophrenia is highly demanded, for which traceable immune mediators in blood could be promising candidates. We aimed to gather the best findings of neuroinflammatory markers for first-episode psychosis (FEP). METHODS: We performed an extensive narrative review of online literature on inflammation-related markers found in human FEP patients only. RESULTS: Changes to cytokine levels have been increasingly reported in schizophrenia. The peripheral levels of IL-1 (or its receptor antagonist), soluble IL-2 receptor, IL-4, IL-6, IL-8, and TNF-α have been frequently reported as increased in FEP, in a suggestive continuum from high-risk stages for psychosis. Microglia and astrocytes establish the link between this immune signalling and the synthesis of noxious tryptophan catabolism products, that cause structural damage and directly hamper normal neurotransmission. Amongst these, only 3-hydroxykynurenine has been consistently described in the blood of FEP patients. CONCLUSION: Peripheral molecules stemming from brain inflammation might provide insightful biomarkers of schizophrenia, as early as FEP or even prodromal phases, although more time- and clinically-adjusted studies are essential for their validation.
Astrocytes ; Biomarkers ; Encephalitis ; Humans ; Interleukin-1 ; Interleukin-4 ; Interleukin-6 ; Interleukin-8 ; Metabolism ; Methods ; Microglia ; Polytetrafluoroethylene ; Psychotic Disorders ; Receptors, Interleukin-2 ; Schizophrenia ; Synaptic Transmission ; Tryptophan

PURPOSE: To evaluate the expression of chemokine and chemokine receptors in the aqueous humor (AH) of patients with recurrent anterior uveitis (AU) in terms of HLA-B-27-association. METHODS: Patients with endogenous uveitis were recruited from the uveitis clinic at Seoul National University Hospital. AH and peripheral blood (PB) were obtained from each patient. The expression of chemokine receptors in T-cells from AH and PB was measured using flow cytometric analysis. Interleukin (IL)-8, interferon-gammainducible protein (IP)-10, and regulated-on-expression, normal T-cell expressed and secreted (RANTES) levels of PB and AH were measured. The expression of chemokine receptor and chemokine levels in PB and AH were compared between HLA-B27-associated AU and idiopathic AU patients. RESULTS: Seventeen patients with HLA-B27-associated AU, 14 patients with idiopathic AU and 5 healthy controls were included in this study. IL-8 and IP-10 levels of AH were shown to be increased more than in PB, and intraocular concentrations of IL-8 and IP-10 were higher in patients with HLA-B27-associated AU than in idiopathic AU patients. RANTES levels in AH were significantly lower than in PB for all groups. In all groups, the expression of chemokine receptor in AH increased more than in PB. CONCLUSIONS: The results from this study show chemokine may play an important role in inflammation in patients with AU. This implies that the chemokine environment may be different in terms of HLA-B-27-association.
Aqueous Humor ; Chemokine CCL5 ; Humans ; Inflammation ; Interleukin-8 ; Interleukins ; Receptors, Chemokine ; T-Lymphocytes ; Uveitis ; Uveitis, Anterior

OBJECTIVE: To investigate the clinical value of expression level of interleukin-2 receptor (IL-2R) and interleukin-8 (IL-8) in the fever patients with hematological malignancies. METHODS: A total of 121 inpatients in the First Affiliated Hospital of Anhui Medical University from April 2018 to October 2019 were enrolled in this study. The patients were separated into infection group (61 cases) and non-infection group (60 cases). In the meantime, 40 healthy people without fever or infection in the hospital for physical examination were set as matched group. C-reactive protein (CRP), procalcitonin (PCT), and cytokines were detected in all the patients with fever after admission and infection control. While, blood samples were taken from healthy people during physical examination. RESULTS: The expression levels of IL-2R in infection group were higher than those in the control group (P<0.001), and the level of serum IL-2R in infection group was also higher than that in the non-infection group (P<0.05). Based on Spearman analysis, in patients with malignant hematologic disease, serum IL-2R level was positively correlated with CRP (r=0.557, P<0.001) and IL-8 (r=0.479, P<0.001), and IL-8 level was positively correlated with CRP (r=0.318, P<0.001). Compared with the non-infection group, the area under the curve (AUC) for the level of CRP, PCT, and IL-2R of the infection group was 0.714 (95%CI: 0.623-0.806), 0.765 (95%CI: 0.680-0.851), and 0.761 (95%CI: 0.686-0.836), the sensitivity was 0.705, 0.852, and 0.705, and the specificity was 0.717, 0.70, and 0.60, respectively. While, AUC of CRP+PCT, CRP+IL-2R, PCT+IL-2R, and CRP+PCT+IL-2R was 0.789 (95%CI: 0.712-0.866), 0.702 (95%CI: 0.623-0.782), 0.757 (95%CI: 0.677-0.838), and 0.789 (95%CI: 0.712-0.866), the sensitivity was 0.738, 0.934, 0.705, and 0.738, and the specificity was 0.840, 0.470, 0.810, and 0.840, respectively. CONCLUSION CRP, PCT, IL-2R, and IL-8 are useful parameters for diagnosis of the infectious fever in patients with hematological malignancies, which provides the basis of initial diagnosis and rational use of antibioties for clinician.
Biomarkers ; C-Reactive Protein ; Calcitonin ; Calcitonin Gene-Related Peptide ; Hematologic Neoplasms ; Humans ; Interleukin-8 ; Protein Precursors ; Receptors, Interleukin-2 ; Sepsis

Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NFkB, ROCK and PKC pathways. In the case of PKC activation, it was observed that PKCδ and PKCμ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve PKCδ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.
Breast Neoplasms* ; Breast* ; Culture Media, Conditioned ; Cytokines ; Interleukin-11 ; Interleukin-8 ; Neoplasm Metastasis ; Osteoclasts ; Receptors, Lysophosphatidic Acid

PURPOSE: Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes. MATERIALS AND METHODS: This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1beta, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method. RESULTS: Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2- tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)+/progesterone receptor (PR)+ tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2- tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER+/PR+ tumors (p=0.022). CONCLUSION: We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.
Breast ; Breast Neoplasms ; Chemokine CCL2 ; Cytokines ; Estrogens ; Follow-Up Studies ; Humans ; Inflammation ; Interleukin-6 ; Interleukin-8 ; Leptin ; Prognosis ; Prospective Studies ; Receptors, Estrogen ; Receptors, Progesterone ; Recurrence ; Tumor Microenvironment

BACKGROUND: The assay of cytokines and their soluble receptors in the synovial fluid of inflammatory arthropathy may be useful in studying pathogenetic and immunoregulatory mechanisms of different arthritis. The aim of this study is to investigate cytokine profiles in rheumatoid arthritis and to find the characteristic pattern of cytokine concentration in rheumatoid arthritis according to the clinical manifestations. METHODS: We measured the concentration of TNF-alpha, IL-1 beta, IL-2, IL-6, IL-8 and IL-10, soluble TNF receptor I, II, IL-1 soluble receptor 2 and IL-6 soluble receptor in synovial fluid from the patients with rheumatoid arthritis using ELISA method. We compared these data with result from osteoarthritis patients. In rheumatoid arthritis, we investigated differences of cytokine profile according to clinical manifestations such as duration of disease, radiographic bone erosions and existence of rheumatoid factor. RESULTS: All of the concentrations of cytokines except IL-2 were significantly elevated in synovial fluid of rheumatoid arthritis than osteoarthritis. When we grouped RA patients according to existence of rheumatoid factor and compared the concentration of cytokines, there were no significant differences between seropositive and seronegative group. We also compared early and late disease, and erosive and non-erosive group but there were no significant differences in cytokine level. CONCLUSION: Our data support the results from other studies that concentration of pro-inflammatory or anti-inflammatory cytokines were elevated in rheumatoid arthritis than osteoarthritis. However, we cannot find the relationship between clinical findings and cytokine profiles in joint fluid.
Arthritis ; Arthritis, Rheumatoid* ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Humans ; Interleukin-1 ; Interleukin-10 ; Interleukin-1beta ; Interleukin-2 ; Interleukin-6 ; Interleukin-8 ; Joints ; Osteoarthritis ; Receptors, Tumor Necrosis Factor ; Rheumatoid Factor ; Synovial Fluid* ; Tumor Necrosis Factor-alpha

Leptin is one of the adipocytokines produced from adipose tissue but its functions in periodontal tissue have not previously been investigated. In our current study, we examined the effects of leptin on the expression of interleukin (IL)-6 and IL-8 in periodontal ligament (PDL) cells and gingival fibroblasts. Leptin receptor expression was evaluated by RT-PCR and the production of cytokines was measured by ELISA. The phosphorylation of Akt and Erk1/2 was assessed by western blotting. mRNA of long and short form leptin receptors were detected in both PDL cells and gingival fibroblasts. Leptin was found to increase the production of IL-6 and IL-8 in both of these cell types, an effect which was not blocked by polymyxin B, an inhibitor of lipopolysaccharide (LPS). Leptin did not alter the production of IL-6 and IL-8 induced by LPS in PDL cells but increased Akt and Erk1/2 phosphorylation in these cells. These results suggest that leptin acts as an inducer of IL-6 and IL-8 in PDL cells and gingival fibroblasts.
Adipokines ; Adipose Tissue ; Blotting, Western ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Fibroblasts ; Interleukin-6 ; Interleukin-8 ; Interleukins ; Leptin ; Periodontal Ligament ; Phosphorylation ; Polymyxin B ; Receptors, Leptin ; RNA, Messenger