IL-6 is a multifunctional cytokine and involved in variety of carcinogenesis. However, the association between IL-6 and sporadic colorectal cancer has not been fully explained. Here, we investigated the role of IL-6 s...IL-6 is a multifunctional cytokine and involved in variety of carcinogenesis. However, the association between IL-6 and sporadic colorectal cancer has not been fully explained. Here, we investigated the role of IL-6 signaling and the cytokine network in sporadic colorectal cancer. We investigated the serum IL-6 levels in patients with sporadic colorectal adenoma, cancer patients, and normal controls. In addition, the expressions of IL-6, gp130, and the IL-6 receptor subunit were investigated in biopsy specimens collected from these subjects. Furthermore, the expressions of CXCL7 and CXCR2, a chemokine and its receptor involved in IL-6 production, were also investigated. We observed an elevated level of serum IL-6 in colorectal cancer patients and an increased expression of IL-6 in colorectal cancer tissues, compared with the levels in a control group and in patients with adenoma. The phosphorylation of gp130 was also increased in the colorectal cancer tissues, compared with that in control and adenoma tissues. The expressions of CXCL7 and CXCR2 in the colorectal cancer tissues were also higher than those in control and adenoma tissues. IL-6 signaling is involved in sporadic colorectal cancer. In addition, the increased expressions of CXCL7 and CXCR2 might, in turn, increase the expression of IL-6 in colorectal cancer. Further studies are required to elucidate the function of the IL-6 signaling and the cytokine network in sporadic colorectal cancer.展开更多
We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOM...We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from <em>C</em>. <em>muridarum</em> elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to <em>C</em>. <em>muridarum</em> nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P < 0.001) and <em>C</em>. <em>muridarum</em> EBs (P < 0.001), when compared to the adjuvant alone group. Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA) + LNP were higher as compared to the MPLA + DDA group (P < 0.001) except for (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + DDA) vs (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + LNP) for both <em>C</em>. <em>muridarum</em> EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-<em>γ</em>/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with <em>Chlamydia</em> antigens also showed protection from <em>C</em>. <em>muridarum</em> challenge, by reduction in bacterial shedding for all groups (P < 0.003) compared to shedding from the adjuvant control. Both vaccine formulations generated robust immunological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.展开更多
文摘IL-6 is a multifunctional cytokine and involved in variety of carcinogenesis. However, the association between IL-6 and sporadic colorectal cancer has not been fully explained. Here, we investigated the role of IL-6 signaling and the cytokine network in sporadic colorectal cancer. We investigated the serum IL-6 levels in patients with sporadic colorectal adenoma, cancer patients, and normal controls. In addition, the expressions of IL-6, gp130, and the IL-6 receptor subunit were investigated in biopsy specimens collected from these subjects. Furthermore, the expressions of CXCL7 and CXCR2, a chemokine and its receptor involved in IL-6 production, were also investigated. We observed an elevated level of serum IL-6 in colorectal cancer patients and an increased expression of IL-6 in colorectal cancer tissues, compared with the levels in a control group and in patients with adenoma. The phosphorylation of gp130 was also increased in the colorectal cancer tissues, compared with that in control and adenoma tissues. The expressions of CXCL7 and CXCR2 in the colorectal cancer tissues were also higher than those in control and adenoma tissues. IL-6 signaling is involved in sporadic colorectal cancer. In addition, the increased expressions of CXCL7 and CXCR2 might, in turn, increase the expression of IL-6 in colorectal cancer. Further studies are required to elucidate the function of the IL-6 signaling and the cytokine network in sporadic colorectal cancer.
文摘We evaluated novel Chlamydial vaccines, consisting of major outer membrane protein (MOMP) alone or in combination with polymorphic membrane proteins D (PmpD) and G (PmpG) using a C57BL/6 mouse model. Native MOMP (nMOMP) isolated from <em>C</em>. <em>muridarum</em> elementary bodies (EBs) and recombinant PmpD and PmpG proteins were adjuvanted with Monophosphoryl lipid A (MPLA), with either lipid nanoparticles (LNPs) or the cationic lipid dimethyldioctadecylammonium bromide (DDA). Antibody titers to <em>C</em>. <em>muridarum</em> nMOMP, and EBs were evaluated by ELISA, and T-cell responses were analyzed by intracellular cytokine staining (ICS). Protection from challenge was determined by qPCR. Vaccine immunized mice showed significantly higher antibody titers to nMOMP (P < 0.001) and <em>C</em>. <em>muridarum</em> EBs (P < 0.001), when compared to the adjuvant alone group. Antibody titers in vaccine groups with Monophosphoryl lipid A (MPLA) + LNP were higher as compared to the MPLA + DDA group (P < 0.001) except for (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + DDA) vs (Cm nMOMP + PmpG + PmpD p73 + PmpD p82 + MPLA + LNP) for both <em>C</em>. <em>muridarum</em> EBs and PmpG. ICS analysis showed more robust CD4 + T-cell responses (IFN-<em>γ</em>/IL-2/TNF-a) in the DDA and LNP groups compared to the adjuvant alone group. The DDA + MPLA gave robust Th17 responses in comparison to MPLA and LNP group. Mice immunized with <em>Chlamydia</em> antigens also showed protection from <em>C</em>. <em>muridarum</em> challenge, by reduction in bacterial shedding for all groups (P < 0.003) compared to shedding from the adjuvant control. Both vaccine formulations generated robust immunological responses, and both were protective by reducing bacterial shedding after challenge. This data indicates equal protection can be achieved without the induction of Th17 responses.
