Anti-IL6 monoclonal antibody, clone NR3-40D4

Airborne pollutants have detrimental effect on the human body and the environment. Diesel exhaust particles (DEPs) are known to be major component of particulate matter (PM) and cause respiratory diseases and neurotoxicity. However, the effects of air pollutants on the sensory nervous system, especially on the olfactory sense, have not been well studied. Herein, we aimed to explore DEPinduced changes in the olfactory perception process. Olfactory sensitivity test was performed after DEP inhalation in mice. Microarray was conducted to determine the differentially expressed genes, which were then utilized to build a network focused on neurotoxicity. Exposure to DEPs significantly reduced sniffing in mice, indicating a disturbance in the olfactory perception process. Through network analysis, we proposed five genes (Cfap69, Cyp26b1, Il1b, Il6, and Synpr) as biomarker candidates for DEP-mediated olfactory dysfunction. Changes in their expression might provoke malfunction of sensory transduction by inhibiting olfactory receptors, neurite outgrowth, and axonal guidance as well as lead to failure of recovery from neuroinflammatory damage through inhibition of nerve regeneration. Thus, we suggest the potential mechanism underlying DEPs-mediated olfactory disorders using genomic approach. Our study will be helpful to future researchers to assess an individual's olfactory vulnerability following exposure to inhalational environmental hazards.

BACKGROUND AND AIMS To date, conflicting data exist as to whether hepatitis B virus (HBV) has the ability to induce innate immune responses. Here, we investigated cellular changes after the first contact between HBV and primary human hepatocytes (PHH)in vitroandin vivo. APPROACH AND RESULTS The exposure of PHH to HBV particles resulted in nuclear translocation of NF kappa B, followed by the expression and secretion of inflammatory cytokines (IL [interleukin] 1B, IL6, and TNF [tumor necrosis factor]). Ultraviolet irradiation of viral particles suppressed HBV infectivity but not the induction of cytokines in PHH, suggesting that the inoculum contains the immune-inducing agent. Purified HBV particles on the whole, which were prepared from HBV DNA-positive and protein-rich fractions after heparin column separation, still had immune-inducing capacity in PHH. The HBV-induced gene expression profile was similar to that induced by toll-like receptor 2 (TLR2) ligand Pam3Cys, but different from those induced by the viral sensors TLR3 or TLR7-9. Treatment of PHH with both HBV particles and Pam3Cys led to phosphorylation of ERK (extracellular signal-regulated kinase), JNK, and p38 mitogen-activated protein kinases as well as NF kappa B (nuclear factor kappa B). Finally, HBV-induced gene expression could be neutralized by TLR2-specific antibodies. Of note, pretreatment with an HBV entry inhibitor attenuated the TLR2-mediated response to HBV, suggesting a receptor binding-related mechanism. In liver-humanized uPA/severe combined immunodeficient (SCID)/beige mice challenged with HBVin vivo, immune induction could only marginally be seen. CONCLUSIONS PHHs are able to sense HBV particles through TLR2, leading to an activation of anti-HBV immune responsesin vitro. These findings challenge the previously described stealth properties of HBV.