Repeated ozone exposure exacerbates insulin resistance and activates innate immune response in genetically susceptible mice

Abstract

Background Inhaled ozone (O3) has been demonstrated as a harmful pollutant and associated with chronic inflammatory diseases such as diabetes and vascular disorders. However, the underlying mechanisms by which O3 mediates harmful effects are poorly understood. Objectives To investigate the effect of O3 exposure on glucose intolerance, immune activation and underlying mechanisms in a genetically susceptible mouse model. Methods Diabetes-prone KK mice were exposed to filtered air (FA), or O3 (0.5 ppm) for 13 consecutive weekdays (4 h/day). Insulin tolerance test (ITT) was performed following the last exposure. Plasma insulin, adiponectin, and leptin were measured by ELISA. Pathologic changes were examined by H&E and oil-red-o staining. Inflammatory responses were detected using flow cytometry and real-time PCR. Results KK mice exposed to O3 displayed an impaired insulin response. Plasma insulin and leptin levels were reduced in O3-exposed mice. Three-week exposure to O3 induced lung inflammation and increased monocytes/macrophages in both blood and visceral adipose tissue. Inflammatory monocytes/macrophages increased both systemically and locally. CD4+ T cell activation was also enhanced by the exposure of O3 although the relative percentage of CD4+ T cell decreased in blood and adipose tissue. Multiple inflammatory genes including CXCL-11, IFN-γ, TNFα, IL-12, and iNOS were up-regulated in visceral adipose tissue. Furthermore, the expression of oxidative stress-related genes such as Cox4, Cox5a, Scd1, Nrf1, and Nrf2, increased in visceral adipose tissue of O3-exposed mice. Conclusions Repeated O3 inhalation induces oxidative stress, adipose inflammation and insulin resistance.

Understanding the Intersection of Environmental Pollution, Pneumonia, and Inflammation: Does Gender Play a Role?

“…Studies conducted in several countries, such as Europe, America, and Asia reported strong associations among exposure to air pollutants, insulin resistance, obesity, and diabetes with women overrepresented in the affected groups [165][166][167][168][169][170]. These findings have also been recapitulated in animal models, where exposure to particulate matter resulted in increased insulin resistance followed by a high-fat diet [171][172][173], and these effects were associated with inflammation triggered by mechanisms involving pulmonary oxidative stress [174].…”

TmRelish is required for regulating the antimicrobial responses to Escherichia coli and Staphylococcus aureus in Tenebrio molitor

“…DmRelish homologues have been identified in other insects where they participate in the regulation of AMP genes in response to pathogenic infections. Relish1 and Relish2 from Anopheles gambiae and Aedes aegypti, respectively, are key transcriptional activators of diptericin/drosomycin (antifungal defense) and defend against gram-positive S. aureus 16 . The DmRelish homolog of Culex quinquefasciatus is activated by the West Nile Virus (WNV), resulting in the triggering of an antiviral response 17 .…”

“…Bombyx mori Relish encodes BmRelish1 and BmRelish2 (dominant negative factor of BmRelish1), which activate or inhibit cecropinB1, respectively 18 . The Manduca sexta Relish isoforms MsRel2A and MsRel2B have also been shown to induce the transcription of AMP genes 16 . Furthermore, Relish silencing in the adult honey bee, Apis mellifera, infected with Escherichia coli reduced the levels of abaecin and hymenoptaecin mRNA expression, but not defensin-1 19 .…”

The antibacterial effect of topical ozone on the treatment of MRSA skin infection

“…Now ozone has been used for treatment of open wounds, Herpes Zoster and Herpes Simplex ( 9 , 10 ), because of its anti-microorganism effectiveness ( 11 ). Additionally, ozone has other advantages like such as improving wound healing, enhancing immune, no side effect, no-toxic, environmental friendly and high efficacy ( 12 ). A few studies have shown that ozone therapy is efficient in killing many kinds of microorganisms, such as S. aureus , Streptococci spp, Escherichia coli , Enterococcus faecalis , and P. aeruginosa ( 13 , 14 ).…”