Archives

  • 2018-07
  • 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
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • br Material and methods br

    2022-06-27


    Material and methods
    Results
    Discussion Propofol is commonly used in operation rooms or intensive care units (ICUs) for critically ill patients. Various clinical trials have demonstrated that the antioxidant, anti-inflammatory, and free-radical-scavenging properties of propofol can provide clinical benefits. For examples, the use of propofol has been reported to reduce the incidence of postoperative cognitive dysfunction, maintain an appropriate hemodynamic status, shorten ICU stays, and increase the lung compliance of patients who underwent major surgery or cardio-pulmonary bypass [28], [29], [30], [31], [32]. Nevertheless, the detailed molecular mechanism that governs these protective effects of propofol is still incompletely understood. In a previous study, we demonstrated that propofol inhibits fMLF-induced neutrophil activation by blocking FPR1 [8]. However, fMLF, which is an exogenous bacterial formylated peptide, is rarely involved in the early stage of sterile tissue injury. The present study illustrated that propofol competitively inhibits the interaction between FPR1 and fMMYALF, which is a mitochondria-derived DAMP released from damaged TAME [22], [33], [34]. Therefore, propofol can reduce superoxide production and associated ROS formation, elastase release, and cell migration, which are all inflammatory responses of neutrophils that can be observed in critically-ill patients caused by traumatic or surgical-associated injury. The human immune is a complex system whose primary aim is to protect human the body from invading pathogens. To achieve this aim, recognition of pathogenic microbes is the first and most critical step, followed by the initiation of a series of responses required for eliminating the invading pathogens. Nevertheless, while invading pathogens that cause tissue injury must be eliminated, the commensal microorganisms that are required for host survival should be tolerated. In addition, the immune system plays a crucial role in maintaining hemostatic tissue function. Sterile tissue injury arising from traumatic or surgery-associated injury must be detected and repaired. In other words, with the emergence of the “danger model” in the scientific community, researchers have come to understand that the immune system depends on various pattern-recognition receptors to distinguish danger and nondanger patterns, rather than self and nonself patterns [35]. The common causes of critical illness, including sepsis, trauma, surgery-related cell damage, hypoxia, and ischemia, also cause uncontrolled cell or tissue damage. Consequently, intracellular molecules, some of which are considered as DAMPs, are either actively or passively discharged into the surrounding tissue and circulation [35], [36]. Moreover, because critically ill patients exhibit immune-associated complications, DAMPs have crucial implications in the prognosis of these patients and are considered possible therapeutic targets for anti-inflammatory compounds. In the past decade, studies have demonstrated that the mitochondrial molecules released into circulation act as DAMPs [37]; therefore, they contribute to DAMP-mediated immune stimulation [22], [33], [37]. Mitochondria originated from engulfed prokaryotic cells [38], [39]. Mitochondrial protein synthesis is similar to that of their prokaryotic ancestor and begins with the N-formyl methionine residue [22], [40], which is absent in the cytosol. The fMMYALF is an N-formyl peptide that corresponds to the N terminus of mitochondrial NADH dehydrogenase subunit 6. Prior studies have reported that fMMYALF, similar to fMLF of prokaryotic origin, is a portent activator that stimulates immune effector cells via FPRs [21], [22], [41]. It induces p38, p44, and p42 MAPK phosphorylation, resulting in the release of proinflammatory signals, including matrix metalloproteinase-8 and interleukin 8 [22], [37]. Moreover, recent studies found that the level of mitochondria-derived formylated peptides is increased in bronchoalveolar lavage fluid and serum of patients with acute respiratory TAME distress syndrome (ARDS) [23]. Considering the importance of mitochondrial N-formylated peptides in ARDS, we used the fMMYALF for human neutrophil stimulation in this study. Our results suggest that propofol may have therapeutic benefits to attenuate endogenous N-formylated peptides-mediated inflammatory diseases.