Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-07
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • br Materials and methods br Results Using an gene

    2022-05-20


    Materials and methods
    Results Using an 84 gene Th1-Th2-Th3 cytokine profile, 17 genes were significantly up-regulated in PBMC one week post-marathon compared to pre-marathon samples (Table 1). Eight genes were down-regulated among various subjects but none consistently enough to achieve statistical significance (Table 2 and supplemental Table 1). It is noted that there was a trend of down-regulation of two Th1 related genes, T-bet and STAT1 (p=0.089 and 0.093, respectively).
    Discussion Extreme exercise can potentially have adverse impact on host immunity (Shepard and Shek, 1996, Barrett et al., 2012). Previous studies have demonstrated an increased rate of URTI symptoms in marathon participants for various reported time periods following a marathon race (Nieman et al., 1990, Peters and Bateman, 1983). Robson-Ansley et al. (2012) reported that marathon runners were more likely to develop a URTI compared to nonparticipants living in the same household. Animal studies have demonstrated that antiviral-specific T cell responses are significantly inhibited by exhaustive exercise (Kohut et al., 2001, Kapasi et al., 2005). It has been hypothesized that even temporary altered immunity induced by exhaustive exercise can increase susceptibility to infection and that decreased performance in exercise is associated with URTI (Walsh et al., 2011). However, the precise immune mechanisms responsible for the increased susceptibility to URTI have not been well documented. In this study using PCR Array technology, our results demonstrated that a physical stressor, namely the completion of a marathon race, induced a shift in the Th1/Th2 balance to Th2 predominance. A decreased Th1/Th2 ratio has been associated with increased susceptibility to URTI following exhaustive physical exercise such as completing a marathon (Suzuki et al., 2002, Suzuki et al., 2003). The Th1/Th2 balance is important in maintaining host immune health (Kidd, 2003). Th1 Busulfan promote resistance to intracellular pathogens, and secrete cytokines such as IFN-γ, a major cytokine associated with host resistance against viral infections. Th2 cells promote resistance to extracellular pathogens and, importantly to the current study, antagonize the production and activity of Th1 cytokines including IFN-γ (Agnello et al., 2003, Romagnani, 2006). Thus, an altered Th1/Th2 balance can influence host susceptibility to a variety of immune-mediated diseases including allergy, autoimmunity and increased infections (Matsuzaki et al., 2005, Marshall, 2011). The Human Th1-Th2-Th3 RT2 Profiler PCR Array examines the expression of 84 genes which are related with Th cell immune responses. Busulfan Our results showed that 17 of 84 genes were significantly altered in the study population one week post-marathon compared to pre-marathon samples. Among up-regulated genes, only 2 (CXCR3 and IRF1) out of 21 genes were Th1 related, whereas 10 out of 29 genes were Th2 related genes including IL4 and GATA3. Another five up-regulated genes reflected CD4+ T cell marker or T cell activation genes (out of 32 genes) which can be involved in either Th1 or Th2 cell activation. In contrast, several genes were down-regulated but did not reach significant differences. Of importance, there was a trend of down-regulation of two Th1 related genes, T-bet and STAT1 (p=0.089 and 0.093, respectively). These data should be verified by real-time PCR with a larger sample size in future studies. CCAAT/enhancer binding proteins (CEBPs) are transcription factors that involve in dimerization and DNA binding (Ramji and Foka, 2002). CEBPβ was first identified to regulate gene transcription in response to IL-1 and IL-6 (Akira et al., 1990, Poli et al., 1990). This regulatory protein is important in immune and inflammatory responses. Our study showed that CEBPβ expression was increased post-marathon compared to pre-marathon supporting the notion that altered CEBPβ may enhance Th2 cell response (Huber et al., 2012). In addition, CD28 and CD86 were also up-regulated post-marathon. CD28 and CD86 are costimulatory molecules which are essential in the regulation of Th1 and Th2 cytokine production. CD28 interacts with two ligands on antigen presenting cells, CD80 and CD86, and plays a pivotal role in the costimulatory signal pathway for T cell activation and regulation (Sharpe and Freeman, 2002, Salomon and Bluestone, 2001, Alegre and Frauwirth, 2001). It has been reported that CD28 binding with CD80 preferentially activates Th1 cells while binding with CD86 activates Th2 cells (Bashian et al., 1997). The increased expression of CD28 and CD86 mRNA in post-marathon samples provide further evidence to explain the mechanisms for a preferential activation of Th2 cells by this physical stressor. The PCR Array data indicate more Th2 and Th2-related genes were activated after a marathon compared to Th1 genes. Although activation of specific Th genes is important in the immune response to specific antigens, the Th1/Th2 balance is more pivotal in the overall immunomodulatory process (Glaser and Kiecolt-Glaser, 2005, Marshall, 2011). We had measured Th gene expression profile one week after race to avoid immune changes that are known to happen as a result of inflammation from the race itself. One week after a marathon, there was little change in IFN-γ mRNA level but IL-4 mRNA expression was significantly increased. Thus, the IFN-γ/IL4 mRNA balance was shifted toward a predominant Th2 response. Our previous study examined cytokine changes at the protein level of both IFNg and IL4 in PBMC gated on CD3+CD8− and CD3−CD8+ cells (Rehm et al., 2013). Th2 (CD3+CD8−IFNg−IL4+) cells were significantly increased pre-race compared to a 4 week prior baseline sample and continued to increase one week post-marathon resulting in a reduced Th1/Th2 ratio which is consistent with our more mechanistic-based gene array study results. Gene expression also revealed that transcription factors T-bet (TBX21) and GATA-3 expression were altered one week post-marathon.