Cytokines are secreted by various cell types and act as critical mediators in many physiological processes, including immune response and tumor progression. Cytokines production is precisely and timely regulated by multiple mechanisms at different levels, ranging from transcriptional to post-transcriptional and posttranslational processes. Monocyte chemoattractant protein-1 induced protein 1 (MCPIP1), a potent immunosuppressive protein, was first described as a transcription factor in monocytes treated with monocyte chemoattractant protein-1 (MCP-1) and subsequently found to possess intrinsic RNase and deubiquitinase activities. MCPIP1 tightly regulates cytokines expression via various functions. Furthermore, cytokines such as interleukin 1 beta (IL-1B) and MCP-1 and inflammatory cytokines inducer lipopolysaccharide (LPS) strongly induce MCPIP1 expression. Mutually regulated MCPIP1 and cytokines form a complicated network in the tumor environment. In this review, we summarize how MCPIP1 and cytokines reciprocally interact and elucidate the effect of the network formed by these components in cancer-related immunity with aim of exploring potential clinical benefits of their mutual regulation.
Chemokine CCL2/immunology* ; Humans ; Interleukin-1beta/immunology* ; Neoplasm Proteins/immunology* ; Neoplasms/pathology* ; Ribonucleases/immunology* ; Transcription Factors/immunology*

OBJECTIVE: To evaluate the efficacy of cis-2-dodecenoic acid (BDSF) in the treatment and prevention of vaginal candidiasis in vivo. METHODS: The activities of different concentrations of BDSF against the virulence factors of Candida albicans (C. albicans) were determined in vitro. An experimental mouse model of Candida vaginitis was treated with 250 μmol/L BDSF. Treatment efficiency was evaluated in accordance with vaginal fungal burden and inflammation symptoms. RESULTS: In vitro experiments indicated that BDSF attenuated the adhesion and damage of C. albicans to epithelial cells by decreasing phospholipase secretion and blocking filament formation. Treatment with 30 μmol/L BDSF reduced the adhesion and damage of C. albicans to epithelial cells by 36.9% and 42.3%, respectively. Treatment with 200 μmol/L BDSF completely inhibited phospholipase activity. In vivo mouse experiments demonstrated that BDSF could effectively eliminate vaginal infection and relieve inflammatory symptoms. Four days of treatment with 250 μmol/L BDSF reduced vaginal fungal loads by 6-fold and depressed inflammation. Moreover, BDSF treatment decreased the expression levels of the inflammatory chemokine-associated genes MCP-1 and IGFBP3 by 2.5- and 2-fold, respectively. CONCLUSION BDSF is a novel alternative drug that can efficiently control vaginal candidiasis by inhibiting the virulence factors of C. albicans.
Animals ; Candida albicans ; drug effects ; metabolism ; pathogenicity ; physiology ; Candidiasis, Vulvovaginal ; drug therapy ; genetics ; immunology ; microbiology ; Chemokine CCL2 ; genetics ; immunology ; Disease Models, Animal ; Fatty Acids, Monounsaturated ; administration & dosage ; Female ; Fungal Proteins ; genetics ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; immunology ; Mice ; Virulence ; drug effects ; Virulence Factors ; genetics ; metabolism

Triptolide (TP) induces severe liver injury, but its hepatotoxicity mechanisms are still unclear. Inflammatory responses may be involved in the pathophysiology. Neutrophils are the first-line immune effectors for sterile and non-sterile inflammatory responses. Thus, the aim of the present study was to investigate the neutrophilic inflammatory response in TP-induced liver injury in C57BL/6 mice. Our results showed that neutrophils were recruited and accumulated in the liver, which was parallel to or slightly after the development of liver injury. Neutrophils induced release of myeloperoxidase and up-regulation of CD11b, which caused cytotoxicity and hepatocyte death. Hepatic expressions of CXL1, TNF-α, IL-6, and MCP1 were increased significantly to regulate neutrophils recruitment and activation. Up-regulation of toll like receptors 4 and 9 also facilitated neutrophils infiltration. Moreover, neutrophils depletion using an anti-Gr1 antibody showed mild protection against TP overdose. These results indicated that neutrophils accumulation might be the secondary response, not the cause of TP-induced liver injury. In conclusion, the inflammatory response including neutrophil infiltration may play a role in TP-induced hepatotoxicity, but may not be severe enough to cause additional liver injury.
Animals ; Chemical and Drug Induced Liver Injury ; etiology ; immunology ; Chemokine CCL2 ; genetics ; immunology ; Diterpenes ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Epoxy Compounds ; adverse effects ; Female ; Humans ; Interleukin-6 ; genetics ; immunology ; Intracellular Signaling Peptides and Proteins ; genetics ; immunology ; Liver ; drug effects ; immunology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration ; drug effects ; Neutrophils ; drug effects ; immunology ; Phenanthrenes ; adverse effects ; Tripterygium ; adverse effects ; chemistry ; Tumor Necrosis Factor-alpha ; genetics ; immunology

OBJECTIVEThe custom-homebuilding company, Cosmic Garden Co. Ltd., located in Okayama City, Japan was established in 1997 and uses specific natural ore powder (SNOP) in wall materials and surveys customers in order to improve allergic symptoms.

METHODSTo investigate the biological effects of SNOP, patients with a pollen allergy were recruited to stay in a room surrounded by cloth containing SNOP (CCSNOP), and their symptoms and various biological parameters were compared with those of individuals staying in a room surrounded by control non-woven cloth (NWC). Each stay lasted 60 min. Before and immediately after the stay, a questionnaire regarding allergic symptoms, as well as POMS (Profile of Mood Status) and blood sampling, was performed. Post-stay minus pre-stay values were calculated and compared between CCSNOP and NWC groups.

RESULTSResults indicated that some symptoms, such as nasal obstruction and lacrimation, improved, and POMS evaluation showed that patients were calmer following a stay in CCSNOP. Relative eosinophils, non-specific Ig E, epidermal growth factor, monocyte chemotactic protein-1, and tumor necrosis factor-α increased following a stay in CCSNOP.

CONCLUSIONThis ore powder improved allergic symptoms, and long-term monitoring involving 1 to 2 months may be necessary to fully explore the biological and physical effects of SNOP on allergic patients.

Adult ; Chemokine CCL2 ; immunology ; Clothing ; Female ; Geologic Sediments ; chemistry ; Humans ; Immunoglobulin E ; immunology ; Japan ; Male ; Pollen ; immunology ; Rhinitis, Allergic, Seasonal ; immunology ; therapy ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo study the role of triggering receptor expressed on myeloid cells-1(TREM-1) in the pathogenesis of Kawasaki disease (KD).

METHODSBased on color Doppler examination results, 45 children with KD were classified into two groups: coronary artery lesions (CAL group) and no coronary artery lesions (NCAL group). Fifteen children with fever caused by respiratory infection (fever control group) and fifteen healthy children (normal control group) served as controls. Real-time fluorescence quantitative PCR was used to detect the expression of TREM-1 mRNA and DNAX-activating protein 12 (DAP12) mRNA in peripheral blood mononuclear cells (PBMC). ELISA was used to detect the expression of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1), DAP12, monocyte chemoattractant protein-1(MCP-1), interleukin-8 (IL-8) proteins levels.

RESULTSThe mean serum protein concentrations of sTREM-1 and DAP12 and the expression levels of TREM-1 mRNA and DAP12 mRNA in PBMC in 45 children with KD (KD group) were significantly higher than in the two control groups (P<0.05). The levels of sTREM-1 protein and TREM-1 mRNA in the CAL subgroup were significantly higher than in the NCAL subgroup (P<0.05). The serum protein concentrations of MCP-1 and IL-8 in the KD group were significantly higher than in the two control groups (P<0.05). The MCP-1 protein level in the CAL subgroup was significantly higher than in the NCAL subgroup (P<0.05). In children with KD, there was a positive correlation between serum sTREM-1 and MCP-1 levels (r=0.523, P<0.05).

CONCLUSIONSTREM-1 activation may be involved in the development of KD.

Chemokine CCL2 ; blood ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Interleukin-8 ; blood ; Male ; Membrane Glycoproteins ; blood ; genetics ; physiology ; Mucocutaneous Lymph Node Syndrome ; etiology ; immunology ; RNA, Messenger ; analysis ; Receptors, Immunologic ; blood ; genetics ; physiology ; Triggering Receptor Expressed on Myeloid Cells-1

Vascular adventitial fibroblasts (AF) may play an important role in vascular inflammation. This study was aimed to investigate the expression pattern of inflammatory mediators in AF induced by angiotensin II (AngII) and to explore the effects of AF-derived inflammatory mediators on the adhesion and migration of macrophages both in vitro and in vivo. We used real-time RT-PCR to detect the mRNA expression of inflammatory mediators in cultured AF. The results showed that AngII (1 × 10(-7) mol/L) up-regulated mRNA expression of 4 inflammatory mediators, including P-selectin, ICAM-1, IL-6 and MCP-1, in cultured AF. Western blot analysis or ELISA revealed that AngII up-regulated P-selectin and ICAM-1 protein expression and IL-6 secretion in cultured AF, but did not alter MCP-1 secretion. We further detected the effects of AF-derived inflammatory mediators on the adhesion and chemotaxis of RAW264.7, a macrophage cell line. We found that AF stimulated with AngII could enhance the adhesion of RAW264.7 and the conditioned medium from AngII-stimulated AF could enhance the migration of RAW264.7. Immunofluorescence study showed an enhanced accumulation of CD68 positive cells and the up-regulation of P-selectin, ICAM-1, IL-6 and MCP-1 in aortic adventitia of AngII-infused (200 ng/kg per min for 2 weeks) rats. We concluded that AF may contribute to vascular inflammation via expression of certain inflammatory mediators and the subsequent adhesion and chemotaxis of macrophages.
Adventitia ; drug effects ; Angiotensin II ; pharmacology ; Animals ; Cell Line ; Chemokine CCL2 ; metabolism ; Culture Media, Conditioned ; Fibroblasts ; drug effects ; immunology ; Inflammation ; immunology ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-6 ; metabolism ; Macrophages ; drug effects ; immunology ; Mice ; P-Selectin ; metabolism ; RAW 264.7 Cells ; Rats ; Up-Regulation

The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.
Allergy and Immunology ; Antidepressive Agents ; Brain ; Central Nervous System ; Chemokine CCL2* ; Communicable Diseases ; Cytokines ; Depression ; Depressive Disorder, Major* ; Humans ; Neurons ; Receptors, Cytokine

The immune hypothesis of major depressive disorder (MDD) fits well with the supposed interaction between genetic and environmental factors in disorders with a complicated etiopathogenesis. It has been suggested that infectious diseases are associated with MDD in that cytokines may play a critical role as a key modulator in the transition between infection and the development of MDD. It has been also suggested that antidepressants have immunomodulatory effects on some cytokines and cytokine receptors, although the exact mechanism has not yet been fully elucidated. Among cytokines, monocyte chemoattractant protein-1 (MCP-1) is especially well known and has attracted considerable interest owing to its immunomodulatory functions. MCP-1 is expressed in highly regionalized neuronal areas in the brain, leading to kind of modulation of neuronal activity and neuroendocrine functions commonly seen in patients with MDD. Additionally, it is involved in the control of other cytokines that have been consistently proposed as associated with the development of MDD. It also has a possible role in the neurodegenerative process of a number of central nervous system (CNS) diseases. Hence, this paper draws from the perspective of immunology to offer several suggestions about the role of MPC-1 in the development of MDD.
Allergy and Immunology ; Antidepressive Agents ; Brain ; Central Nervous System ; Chemokine CCL2* ; Communicable Diseases ; Cytokines ; Depression ; Depressive Disorder, Major* ; Humans ; Neurons ; Receptors, Cytokine

OBJECTIVETo observe the effect of Huanglian Jiedu IJecoction (HJU) on systemic and vascular immune responses of high fat diet fed apoE deficient (apoE(-/-)) mice.

METHODSEight wild type C57BL6 mice were recruited as the wild type common food group. Totally 24 apoE(-/-) mice were randomly divided into the ApoE'common food group, the ApoE(-/-) hyperlipidemia group, and the ApoE(-/-) hyperlipidemia plus HJD group, 8 in each group. In the present study, the common food mice and high fat fed mice were fed with a chow diet or a high cholesterol diet for 4 weeks. HJD was given to mice in the ApoE(-/-) hyperlipidemia plus HJD group at the daily dose of 5 g/kg by gastrogavage, while equal volume of pure water was given to mice in the rest groups by gastrogavage. Four weeks later, the plasma levels of blood lipids, the ratio of peripheral blood mononuclear cells, and expressions of Toll-like receptor 4 (TLR-4) and CD36 on the monocytes were detected. The pathological changes and expressions of cytokines in local aorta were detected. The plasma cytokine levels in response to lipopolysaccharide (LPS) were analyzed. Results (1) Compared with the wild type common food group, TO, TG, and LDL-O significantly increased in the ApoE(-/-) common food group (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, TC and LDL-C significantly increased in the hyperlipidemia group (P < 0. 05). There was no statistical difference in each index between the ApoE(-/-) hyperlipidemia group and the ApoE(-/-) hyperlipidemia plus HJD group (P > 0.05). (2) Compared with the wild type common food group, no obvious change of the ratio of peripheral blood mononuclear cells happened, the TLR4 expression level significantly increased in the ApoE'common food group (P < 0. 05). Compared with the ApoE common food group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly increased in the ApoE' hyperlipidemia group (P < 0.05). Compared with the ApoE(-/-) hyperlipidemia group, the ratio of peripheral blood mononuclear cells and the TLR4 expression level significantly decreased. Besides, the CD36 expression level also significantly decreased (P<0.05). (3) After stimulated by LPS for 3 h, compared with the wild type common food group, plasma TNF-ct and IL-b expressions significantly increased in the ApoE(-/-) common food group (P < 0.05). Compared with the ApoE(-/-) common food group, plasma expressions of IL-12, TNF-alpha, MCP-1, and IL-10 increased, but with no statistical difference in the ApoE(-/-) hyperlipidemia group (P > 0.05). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, the MCP-1 expression was significantly down-regulated, while the IL-10 expression significantly increased, showing statistical difference (P < 0.05). Compared with the wild type common food group, mRNA expression levels of IFN-gamma, MCP-1 , TNF-alpha, IL-10, and IL-1beta significantly increased (P < 0. 05, P < 0.01). Compared with the ApoE(-/-) common food group, not only mRNA expression levels of IFN-gamma, MCP-1, TNF-alpha, and IL-1beta, further significantly increased, but also IL-12, IL-10, and TGF-beta significantly increased (P < 0. 05, P < 0. 01). After 4-week intervention of HJD, compared with the ApoE(-/-) hyperlipidemia group, mRNA expression levels of MCP-1, TNF-alpha, IL-1beta, and IL-12 significantly decreased in the ApoE(-/-) hyperlipidemia plus HJD group (P < 0.05, P < 0.01).

CONCLUSIONSHigh fat diet induced systemic reaction and inflammatory reactions of local vessels. The local inflammatory response of vessels exceeded systemic inflammatory response. Intervention of HJD could attenuate inflammatory response, especially in local arteries. Meanwhile, it enhanced systemic anti-inflammatory reactions.

Animals ; Aorta ; pathology ; Apolipoproteins E ; genetics ; CD36 Antigens ; metabolism ; Chemokine CCL2 ; metabolism ; Dietary Fats ; adverse effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hyperlipidemias ; blood ; etiology ; immunology ; Inflammation ; Interleukin-10 ; blood ; Interleukin-12 ; blood ; Interleukin-1beta ; blood ; Leukocytes, Mononuclear ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Systemic Inflammatory Response Syndrome ; blood ; etiology ; immunology ; Toll-Like Receptor 4 ; metabolism ; Transforming Growth Factor beta ; blood ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDThe Fc receptor associated pathway might improve the immune responses against hepatitis B virus (HBV) as previously described by us. In addition, the Flt3 ligand (FL) has been reported to potentiate antigen presenting cells in vivo and may act as a potential adjuvant to boost antigen-specific immune responses. In this study, the immune efficacies of a set of fusion proteins of HBsAg and Fc and/or FL were evaluated in HBsAg transgenic mice.

METHODSThe fusion proteins composed of HBsAg and the Fc domain of murine IgG1 (HBsAg-Fc) and/or the Flt3 ligand, and yeast-derived recombinant HBsAg were used as immunogen to immunize HBsAg transgenic mice, respectively. Serum and liver HBsAg levels, serum anti-HBsAg and cytokine profile, and the activities of alanine aminotransferase (ALT)/AST were investigated after immunization.

RESULTSAfter six injections, the most pronounced decrease in serum and liver HBsAg levels was observed in the HBsAg-Fc immunized group. In addition, serum Th1 cytokines and ALT/AST activities were highest in this group, indicating an effective induction of a favorable cellular immune response. Interestingly, the fusion protein containing HBsAg-Fc and the Flt3 ligand stimulated an alternative Th1-type immune response featured with high level productions of tumor necrosis factor α (TNF-α) and monocyte chemoabstractant protein 1 (MCP-1), causing a more severe cytotoxicity in hepatocytes while showed less effective in reducing serum HBsAg level.

CONCLUSIONHBsAg-Fc is effective in eliciting both the humoral and cellular immune responses against HBsAg in HBsAg transgenic mice, which makes it a potential immunogen for the immunotherapy of chronic hepatitis B.

Animals ; Chemokine CCL2 ; metabolism ; Cytokines ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Hepatitis B Surface Antigens ; genetics ; immunology ; metabolism ; Immunity, Cellular ; immunology ; Immunity, Humoral ; immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Receptors, Fc ; genetics ; immunology ; metabolism ; Recombinant Fusion Proteins ; genetics ; immunology ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism