scholarly journals Immunomodulatory Effects of Pentoxifylline: Profiling Data Based on RAW 264.7 Cellular Signaling

2021 ◽  
Vol 11 (17) ◽  
pp. 8273
Author(s):  
Mi Hyun Seo ◽  
Mi Young Eo ◽  
Truc Thi Hoang Nguyen ◽  
Hoon Joo Yang ◽  
Soung Min Kim

Pentoxifylline (PTX) is a methylxanthine derivative that has been developed as an immunomodulatory agent and an improvement of microcirculation. Osteoradionecrosis (ORN) is a serious complication of radiation therapy due to hypovascularity. Coronavirus disease 2019 (COVID-19) has spread globally. Symptoms for this disease include self-limiting respiratory tract illness to severe pneumonia and acute respiratory distress. In this study, the effects of PTX on RAW 264.7 cells were investigated to reveal the possibility of PTX as a therapeutic agent for ORN and COVID-19. To reveal PTX effects at the cellular level, protein expression profiles were analyzed in the PTX-treated RAW 264.7 cells by using immunoprecipitation high-performance liquid chromatography (IP-HPLC). PTX-treated RAW 264.7 cells showed increases in immunity- and osteogenesis-related proteins and concurrent decreases in proliferation-, matrix inflammation-, and cellular apoptosis-related proteins expressions. The IP-HPLC results indicate that PTX plays immunomodulatory roles in RAW 264.7 cells by regulating anti-inflammation-, proliferation-, immunity-, apoptosis-, and osteogenesis-related proteins. These results suggest that PTX may be used as supplement medications for ORN as well as for COVID-19.

2012 ◽  
Vol 40 (04) ◽  
pp. 813-831 ◽  
Author(s):  
You-Chang Oh ◽  
Won-Kyung Cho ◽  
Yun Hee Jeong ◽  
Ga Young Im ◽  
Min Cheol Yang ◽  
...  

Sipjeondaebotang (SJ) has been used as a traditional drug in east-Asian countries. In this study, to provide insight into the biological effects of SJ and SJ fermented by Lactobacillus, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in macrophages. The investigation was focused on whether SJ and fermented SJ could inhibit the production of pro-inflammatory mediators such as prostaglandin (PG) E2 and nitric oxide (NO) as well as the expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB in LPS-stimulated RAW 264.7 cells. We found that SJ modestly inhibited LPS-induced PGE2, NO and TNF-α production as well as the expressions of COX-2 and iNOS. Interestingly, fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, fermented SJ exhibited increased inhibition of p38 MAPK and c-Jun NH2-terminal kinase (JNK) MAPK phosphorylation as well as NF-κB p65 translocation by reduced IκBα degradation compared with either untreated controls or unfermented SJ. High performance liquid chromatography (HPLC) analysis showed fermentation by Lactobacillus increases liquiritigenin and cinnamyl alcohol contained in SJ, which are known for their anti-inflammatory activities. Finally, SJ fermented by Lactobacillus exerted potent anti-inflammatory activity by inhibiting MAPK and NF-κB signaling in RAW 264.7 cells.


PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9202 ◽  
Author(s):  
Sang Shin Lee ◽  
Soung Min Kim ◽  
Yeon Sook Kim ◽  
Suk Keun Lee

Background Bisphosphonate therapy has become a popular treatment for osteoporosis, Paget’s disease, multiple myeloma, osteogenesis imperfecta, myocardial infarction, and cancer despite its serious side effects. Bisphosphonate-induced molecular signaling changes in cells are still not clearly elucidated. Methods As bisphosphonates are primarily engulfed by macrophages, we treated RAW 264.7 cells (a murine macrophage cell line) with pamidronate and investigated global protein expressional changes in cells by immunoprecipitation high performance liquid chromatography (IP-HPLC) using 218 antisera. Results Pamidronate upregulated proliferation-activating proteins associated with p53/Rb/E2F and Wnt/β-catenin pathways, but downregulated the downstream of RAS signaling, pAKT1/2/3, ERK-1, and p-ERK-1, and subsequently suppressed cMyc/MAX/MAD network. However, in situ proliferation index of pamidronate-treated RAW264.7 cells was slightly increased by 3.2% vs. non-treated controls. Pamidronate-treated cells showed increase in the expressions of histone- and DNA methylation-related proteins but decrease of protein translation-related proteins. NFkB signaling was also suppressed as indicated by the down-regulations of p38 and p-p38 and the up-regulation of mTOR, while the protein expressions related to cellular protection, HSP-70, NRF2, JNK-1, and LC3 were upregulated. Consequently, pamidronate downregulated the protein expressions related to immediate inflammation,cellular differentiation, survival, angiogenesis, and osteoclastogenesis, but upregulated PARP-1 and FAS-mediated apoptosis proteins. These observations suggest pamidronate affects global protein expressions in RAW 264.7 cells by stimulating cellular proliferation, protection, and apoptosis but suppressing immediate inflammation, differentiation, osteoclastogenesis, and angiogenesis. Accordingly, pamidronate appears to affect macrophages in several ways eliciting not only its therapeutic effects but also atypical epigenetic modification, protein translation, RAS and NFkB signalings. Therefore, our observations suggest pamidronate-induced protein expressions are dynamic, and the affected proteins should be monitored by IP-HPLC to achieve the therapeutic goals during treatment.


Foods ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3155
Author(s):  
Lijia Zhang ◽  
Mengzhou Yin ◽  
Xi Feng ◽  
Salam A. Ibrahim ◽  
Ying Liu ◽  
...  

In this study, triterpenoid compounds from Poriae Cutis were separated by high-speed countercurrent chromatography (HSCCC) and identified using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS/MS) and nuclear magnetic resonance (NMR). The in vitro anti-inflammatory activities of the purified triterpenoids on RAW 264.7 cells were also investigated. Triterpenoids, poricoic acid B, poricoic acid A, dehydrotrametenolic acid, and dehydroeburicoic acid were obtained; their levels of purity were 90%, 92%, 93%, and 96%, respectively. The results indicated that poricoic acid B had higher anti-inflammatory activity than those of poricoic acid A by inhibiting the generation of NO in lipopolysaccharide (LPS)-induced RAW 264.7 cells. However, dehydrotrametenolic acid and dehydroeburicoic acid had no anti-inflammatory activity. In addition, the production of cytokines (TNF-α, IL-1β, and IL-6) in cells treated with poricoic acid B decreased in a dose-dependent manner in the concentration range from 10 to 40 μg/mL. The results provide evidence for the use of Poriae Cutis as a natural anti-inflammatory agent in medicines and functional foods.


2010 ◽  
Vol 5 (8) ◽  
pp. 1934578X1000500 ◽  
Author(s):  
Ya-Jun Cui ◽  
Shu-Hong Guan ◽  
Li-Xing Feng ◽  
Xiao-Yi Song ◽  
Chao Ma ◽  
...  

The cytotoxicty of 9,11-dehydroergosterol peroxide (DHEP) isolated from the fruiting bodies of Ganoderma lucidum on HeLa cells was studied. DHEP treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with an IC50-value of 8.58 ± 0.98 μM. Morphological changes of DHEP-treated cells indicated that DHEP induced apoptosis in HeLa cells. To identify the cellular targets of DHEP, two-dimensional electrophoresis analysis was performed to compare the protein expression profiles of DHEP-treated cells with that of control cells. Proteins altered in expressional level after DHEP exposure were identified by MALDI-TOF MS/MS. The cytotoxic effect of DHEP was associated with regulated expression of 6 proteins. Stathmin 1 might be an important target-related protein of DHEP. The regulation of stathmin 1 by DHEP treatment was also confirmed by Western blotting.


2009 ◽  
Vol 121 (2) ◽  
pp. 213-220 ◽  
Author(s):  
Hyoung-Seok Jang ◽  
Hwan-Suck Chung ◽  
Eunjung Ko ◽  
Joon-Shik Shin ◽  
Min-Kyu Shin ◽  
...  

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