PGE2 increases inflammatory damage in<i>Escherichia coli</i>-infected bovine endometrial tissue in vitro via the EP4-PKA signaling pathway†

Li, Tingting; Liu, Bo; Guan, Hong; Mao, Wei; Wang, Lingrui; Zhang, Chao; Hai, Lili; Liu, Kun; Cao, Jinshan

doi:10.1093/biolre/ioy162

Cited by 23 publications

(11 citation statements)

References 70 publications

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“…Hence, it does not entirely block the arachidonic pathway from arachidonic acid metabolism via the TXA2S, PGI2S, PGF2S and PGD2S enzymes. Arachidonic acid levels are reduced with MF63, so there may be less CFTR inhibition 61 . This is important, as arachidonic acid levels are known to be elevated in CF patients 60 , 62 .…”

Section: Discussionmentioning

confidence: 99%

The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway

Carlile

Yang

Matthes

et al. 2022

Sci Rep

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Most cases of cystic fibrosis (CF) are caused by class 2 mutations in the cystic fibrosis transmembrane regulator (CFTR). These proteins preserve some channel function but are retained in the endoplasmic reticulum (ER). Partial rescue of the most common CFTR class 2 mutant, F508del-CFTR, has been achieved through the development of pharmacological chaperones (Tezacaftor and Elexacaftor) that bind CFTR directly. However, it is not clear whether these drugs will rescue all class 2 CFTR mutants to a medically relevant level. We have previously shown that the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen can correct F508del-CFTR trafficking. Here, we utilized RNAi and pharmacological inhibitors to determine the mechanism of action of the NSAID glafenine. Using cellular thermal stability assays (CETSAs), we show that it is a proteostasis modulator. Using medicinal chemistry, we identified a derivative with a fourfold increase in CFTR corrector potency. Furthermore, we show that these novel arachidonic acid pathway inhibitors can rescue difficult-to-correct class 2 mutants, such as G85E-CFTR > 13%, that of non-CF cells in well-differentiated HBE cells. Thus, the results suggest that targeting the arachidonic acid pathway may be a profitable way of developing correctors of certain previously hard-to-correct class 2 CFTR mutations.

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Section: Discussionmentioning

confidence: 99%

The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway

Carlile

Yang

Matthes

et al. 2022

Sci Rep

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“…Oxidative stress leads to an excessive accumulation of reactive oxygen species, such as NO and PGE 2 , in activated macrophages that has been observed in both acute and chronic inflammation in a number of disease conditions, including atherosclerosis, obesity and arthritis (31)(32)(33). Inhibition of NO production and PGE 2 accumulation modulates the inflammatory response in macrophages, leading to the reduction of swelling and redness at the infection site (34,35).…”

Section: Discussionmentioning

confidence: 99%

Artemisia iwayomogi (Dowijigi) inhibits lipopolysaccharide‑induced inflammation in RAW264.7 macrophages by suppressing the NF‑κB signaling pathway

et al. 2020

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Inflammatory diseases are an important health concern and have a growing incidence worldwide. Thus, developing novel and safe drugs to treat these disorders remains an important pursuit. Artemisia iwayomogi, locally known as Dowijigi (DJ), is a perennial herb found primarily in Korea and is used to treat various diseases such as hepatitis, inflammation and immune disorders. In the present study, the anti-inflammatory effects of a polyphenolic extract from the DJ flower (PDJ) in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW264.7 cells were investigated. Cell cytotoxicity was assessed using the MTT assay. The production of nitric oxide (NO) and prostaglandin E 2 (PGE 2) was measured by Griess and ELISA analysis, respectively. The expression levels of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) were examined by western blot analysis. Reverse transcription-quantitative PCR was performed to detect the mRNA expression levels of pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1β, as well as COX2 and iNOS. The production of NO and PGE 2 was significantly decreased following treatment with PDJ. The mRNA expression levels of TNFα, IL-6, IL-1β, COX2 and iNOS were significantly decreased in LPS-induced PDJ co-treated cells compared with the group treated with LPS alone. Western blot analysis indicated that PDJ downregulated the LPS-induced expression of iNOS and COX2, as well as the expression of NF-κB proteins. In conclusion, the present study demonstrated that PDJ exerted anti-inflammatory effects in LPS-induced macrophage cells by suppressing the NF-κB signaling pathway. Therefore, PDJ may be used as a potential therapeutic agent in inflammation.

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“…Herein, we report that increased levels of leptin in the lung result in the upregulation of the inflammatory proteins cPLA2α and COX-2 and promote the accumulation of leukocytes. It is suggested that the expression of cPLA2α or COX-2-dependent prostaglandin E2 (PGE2) exacerbates Streptococcus pneumoniae or Escherichia coli-infected damage to the lung and endometrium [35,36]. Moreover, persistent chronic inflammation leads to fibrosis [37,38].…”

Section: Discussionmentioning

confidence: 99%

Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

Hsu¹,

Lin

Chang

et al. 2019

IJMS

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Obesity is a worldwide epidemic problem and correlates to varieties of acute or chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary fibrosis. An increase of leptin, a kind of adipokine, in lean mice plasma has been found to impair immune responses and facilitate the infection of Klebsiella pneumoniae, resulting in increased pneumonia severity. Also, a higher leptin level is found in exhaled breath condensates of obese or asthmatic subjects, compared to healthy ones, suggesting that leptin is involved in the occurrence or exacerbation of lung injury. In previous studies, we showed that leptin stimulated cytosolic phospholipase A2-α (cPLA2α) gene expression in lung alveolar type II cells via mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB)-activated coactivator p300. Herein, we show that the in vivo application of leptin in the respiratory system upregulated the expression of inflammatory proteins cPLA2α and cyclooxygenase-2 (COX-2) together with leukocyte infiltration. Treatment with an ROS scavenger (N-acetylcysteine, NAC), an NADPH oxidase inhibitor (apocynin), or an activating protein (AP)-1 inhibitor (tanshinone IIA) attenuated leptin-mediated cPLA2α/COX-2 expression and leukocyte recruitment in the lung. Leptin increased intracellular oxidative stress in a leptin receptor (OB-R) and NADPH oxidase-dependent manner, leading to the phosphorylation of the AP-1 subunit c-Jun. In summation, leptin increased lung cPLA2α/COX-2 expression and leukocyte recruitment via the NADPH oxidase/ROS/AP-1 pathway. Understanding the inflammatory effects of leptin on the pulmonary system provides opportunities to develop strategies against lung injury related to metabolic syndrome or obesity.

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PGE2 increases inflammatory damage inEscherichia coli-infected bovine endometrial tissue in vitro via the EP4-PKA signaling pathway†

Cited by 23 publications

References 70 publications

The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway

The NSAID glafenine rescues class 2 CFTR mutants via cyclooxygenase 2 inhibition of the arachidonic acid pathway

Artemisia iwayomogi (Dowijigi) inhibits lipopolysaccharide‑induced inflammation in RAW264.7 macrophages by suppressing the NF‑κB signaling pathway

Participation of NADPH Oxidase-Related Reactive Oxygen Species in Leptin-Promoted Pulmonary Inflammation: Regulation of cPLA2α and COX-2 Expression

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