Effects of IS-741, a Synthetic Anti-Inflammatory Agent, on Bleomycin-Induced Lung Injury in Mice

Shimaoka, Yuichi; Tajima, Shunji; Fujimori, Fumio; Yamabayashi, Cristiane; Moriyama, Hiroshi; Tomita, Masaki; Takada, Toshinori; Suzuki, Eiichi; Bando, Masashi; Sugiyama, Yukihiko; Narita, Ichiei

doi:10.1007/s00408-009-9162-6

Cited by 4 publications

(5 citation statements)

References 32 publications

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“…In the present study, we observed no suppression of MPO-positive neutrophil infiltration into the muscularis externa following FUZ treatment after IM. This observation contrasts with prior research on animal models of pancreatitis and colitis, where FUZ treatment led to marked reductions in neutrophil infiltration into inflamed tissues [ 15 , 30 , 40 , 41 ]. Such a discrepancy implies that the LFA-1 activation might play a less pivotal role in neutrophil infiltration during POI.…”

Section: Discussioncontrasting

confidence: 99%

“…The primary limitation of our study is the undetermined blood concentrations of FUZ in mice throughout the experiment. In this study, we administered FUZ 1 hr before and 4 hr after IM based on a previous report using a mouse model of lung injury [ 30 ]. Yet, the pharmacokinetics of FUZ in mice have not been reported, and our study did not confirm that FUZ consistently maintained an effective blood concentration throughout the experimental duration.…”

Section: Discussionmentioning

confidence: 99%

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Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa

KAJI,

IWAOKA,

NAKAMURA

et al. 2023

J. Vet. Med. Sci.

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Postoperative ileus (POI) is a surgical complication that induces emesis and anorexia. Fuzapladib (FUZ), an inhibitor of leukocyte-function-associated antigen type 1 (LFA-1) activation, a leukocyte adhesion molecule, exerts anti-inflammatory effects by inhibiting leukocyte migration into the inflammatory site.In this study, we examined the prophylactic impact of FUZ on POI in a mouse model. POI model mice were generated by intestinal manipulation, and the effect of FUZ on intestinal transit and the infiltration of inflammatory cells into the ileal muscularis externa was assessed. The increased number of macrophages was significantly suppressed by FUZ, whereas the infiltration of neutrophils into the ileal muscularis externa was not sufficiently inhibited in the POI model mice. Additionally, FUZ did not ameliorate delayed gastrointestinal transit in POI model mice. In conclusion, our results suggest that FUZ does not improve delayed gastrointestinal transit but partially inhibits inflammation in the ileal muscularis externa in POI model mice. FUZ may be a potential anti-inflammatory agent for the management of post-surgical inflammation.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa

KAJI,

IWAOKA,

NAKAMURA

et al. 2023

J. Vet. Med. Sci.

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“…Tof1, Csm3 and Mrc1 are all necessary for normal fork progression as well as stable checkpoint fork arrest [8,45], but just Mrc1 is sufficient to guarantee recovery after fork arrest [46]. It was shown that replication forks reveal restart difficulties after HU block in mrc1∆ cells [39].…”

Section: Resultsmentioning

confidence: 99%

“…All three proteins Tof1, Csm3 and Mrc1 are involved in normal fork progression and stable checkpoint fork arrest [8,45], but just Mrc1 is assumed to be responsible for fork rehabilitation after fork arrest [39]. Stalled forks restart much harder in mrc1Δ cells when HU is removed from the media, suggesting a role for Mrc1 to promote stable fork-pausing complex formation and to guarantee recovery after fork arrest.…”

Section: Discussionmentioning

confidence: 99%

The subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3: dynamics and interdependence

et al. 2014

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BackgroundThe S-phase checkpoint aims to prevent cells from generation of extensive single-stranded DNA that predisposes to genome instability. The S. cerevisiae complex Tof1/Csm3/Mrc1 acts to restrain the replicative MCM helicase when DNA synthesis is prohibited. Keeping the replication machinery intact allows restart of the replication fork when the block is relieved. Although the subunits of the Tof1/Csm3/Mrc1 complex are well studied, the impact of every single subunit on the triple complex formation and function needs to be established.FindingsThis work studies the cellular localization and the chromatin binding of GFP-tagged subunits when the complex is intact and when a subunit is missing. We demonstrate that the complex is formed in cell nucleus, not the cytoplasm, as Tof1, Csm3 and Mrc1 enter the nucleus independently from one another. Via in situ chromatin binding assay we show that a Tof1-Csm3 dimer formation and chromatin binding is required to ensure the attachment of Mrc1 to chromatin. Our study indicates that the translocation into the nucleus is not the process to regulate the timing of chromatin association of Mrc1. We also studied the nuclear behavior of Mrc1 subunit in the process of adaptation to the presence hydroxyurea. Our results indicate that after prolonged HU incubation, cells bypass the S-phase checkpoint and proceed throughout the cell cycle. This process is accompanied by Mrc1 chromatin detachment and Rad53 dephosphorylation.ConclusionsIn S. cerevisiae the subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3 independently enter the cell nucleus, where a Tof1-Csm3 dimer is formed to ensure the chromatin binding of Mrc1 and favor DNA replication and S-phase checkpoint fork arrest. In the process of adaptation to the presence of hydroxyurea Mrc1 is detached from chromatin and Rad53 checkpoint activity is diminished in order to allow S-phase checkpoint escape and completion of the cell cycle.

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“…Numerous studies have demonstrated that CysLTs were a kind of potent pro-inflammatory mediator in lung diseases, particularly pulmonary fibrosis and lung inflammation [31][32][33]. In pulmonary fibrotic diseases such as asthma, the production of inflammatory factors such as TGF-β and TNF-α usually tend to increase, which could promote the synthesis of CysLTs (CysLT, LTC4, and LTE4) [34].…”

Section: Discussionmentioning

confidence: 99%

Baicalin Ameliorates Radiation-Induced Lung Injury by Inhibiting the CysLTs/CysLT1 Signaling Pathway

Bao

Wang

Zhu

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Radiation-induced lung injury (RILI) is a common complication of radiotherapy for thoracic tumors. This study investigated the alleviating effect of baicalin (BA) on RILI and its possible mechanism. Methods. RILI model was established by chest irradiation (IR) of C57BL/6 mice for 16 weeks. Different concentrations of BA were administered, and dexamethasone (DXM) was used as a positive control. Then, the lung pathological changes were observed by HE and Masson staining. The levels of TGF-β, TNF-α, IL-1β, IL-6, CysLT, LTC4, and LTE4 were measured by ELISA. The CysLT1 expression was detected by qPCR, immunohistochemistry, and western blot. Type II AEC cells were pretreated with LTD-4 to establish the RILI cell model and intervened with different concentrations of BA. Then, the collagen I protein level was measured by ELISA. The CysLT1 and α-SMA expression were detected by qPCR, immunofluorescence, and western blot. Results. BA could effectively improve lung histopathological changes and pulmonary fibrosis. In vivo, BA could inhibit the levels of TGF-β, TNF-α, IL-1β, and IL-6 and reduce the levels of CysLT, LTC4, and LTE4. In vitro, different concentrations of LTD4 could reduce the viability of type II AEC cells, which could be reversed by the administration of different concentrations of BA. In addition, BA could reduce CysLT1 mRNA, as well as CysLT1 and α-SMA protein levels in vitro and in vivo. Conclusion. BA attenuated lung inflammation and pulmonary fibrosis by inhibiting the CysLTs/CysLT1 pathway, thereby protecting against RILI.

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Effects of IS-741, a Synthetic Anti-Inflammatory Agent, on Bleomycin-Induced Lung Injury in Mice

Cited by 4 publications

References 32 publications

Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa

Fuzapladib reduces postsurgical inflammation in the intestinal muscularis externa

The subunits of the S-phase checkpoint complex Mrc1/Tof1/Csm3: dynamics and interdependence

Baicalin Ameliorates Radiation-Induced Lung Injury by Inhibiting the CysLTs/CysLT1 Signaling Pathway

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