The value and association of CC chemokine receptor 7 expression in non-small cell lung cancer with lymph nodes metastasis

Objective： The aim of this study was to analyze the expression of CC chemokine receptor 7 （CCR7） in pulmonary tumor tissue and metastasized lymph nodes of non-small cell lung cancer （NSCLC）, explore the relationship between the expressions of CCR7 in pulmonary tumor tissue and metastasized lymph nodes, and discuss the significance. Methods： SABC immunohistochemical staining was used to investigate the expression of CCR7 by rabbit anti-human CCR7 monoclonal antibody, and the specimens were 17 cases of adenocarcinoma, 17 cases of squamous cell carcinoma, 12 cases of adenosquamous carcinoma, 4 cases of large cell carcinoma and 28 cases of metastasized lymph nodes of lung cancer. Negative control sections used 5 cases of inflammatory pseudotumor and 20 cases of normal lung tissue. Two independent pathologists observed all the specimens in the high power field （x 400） of microscope by double blind method. Results： （1） The expression of CCR7 in pulmonary tumor tissue was stronger than normal lung tissue （P 〈 0.005）; （2） The expressions of CCR7 in pulmonary tumor tissues and metastasized lymph nodes had no significant differences （P = 0.177）; （3） The expression of CCR7 had correlation with lymph nodes metastasis, and the expression in lymph nodes metastasis group was more than that of no lymph nodes metastasis group （P = 0.016）; （4） Along with the increment of clinical stage, the CCR7 expression had a tendency to increase （P = 0.003）. Conclusion： CCR7 has rich expression in carcinoma cell nests and lymph node metastasis. It demonstrates that CCR7 may be related to the development of lymph node metastasis in NSCLC.

Maraviroc promotes recovery from traumatic brain injury in mice by suppression of neuroinflammation and activation of neurotoxic reactive astrocytes

Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.

Genotypes and polymorphisms of mutant CCR5-△32,CCR2-64I and SDF1-3'A HIV-1 resistance alleles in indigenous Han Chinese

Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.

Dendritic cell migration in inflammation and immunity

Dendritic cells(DCs)are the key link between innate immunity and adaptive immunity and play crucial roles in both the promotion of immune defense and the maintenance of immune tolerance.The trafficking of distinct DC subsets across lymphoid and nonlymphoid tissues is essential for DC-dependent activation and regulation of inflammation and immunity.DC chemotaxis and migration are triggered by interactions between chemokines and their receptors and regulated by multiple intracellular mechanisms,such as protein modification,epigenetic reprogramming,metabolic remodeling,and cytoskeletal rearrangement,in a tissue-specific manner.Dysregulation of DC migration may lead to abnormal positioning or activation of DCs,resulting in an imbalance of immune responses and even immune pathologies,including autoimmune responses,infectious diseases,allergic diseases and tumors.New strategies targeting the migration of distinct DC subsets are being explored for the treatment of inflammatory and infectious diseases and the development of novel DC-based vaccines.In this review,we will discuss the migratory routes and immunological consequences of distinct DC subsets,the molecular basis and regulatory mechanisms of migratory signaling in DCs,and the association of DC migration with the pathogenesis of autoimmune and infectious diseases.