15-Deoxy-Δ12,14-Prostaglandin J2 Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

김정혜,김희선 대한면역학회 2009 Immune Network Vol.9 No.2

Background: 15d-PGJ2 has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-PGJ2 on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-κB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-PGJ2 decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ2 in SHR VSMCs was mediated through PPARγ, and dependent on NF-κB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 on LPSinduced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ2/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARγ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/ LPS-induced IL-8/CXCL8 expression in SHR VSMCs. Background: 15d-PGJ2 has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ2 on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-PGJ2 on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-κB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-PGJ2 decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ2 in SHR VSMCs was mediated through PPARγ, and dependent on NF-κB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ2 on LPSinduced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ2/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-PGJ2 on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARγ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ2/ LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

한국인 구강편평상피세포암종 환자에서 CXCL1과 CXCL2 유전자의 다형성에 관한 연구

강상욱,김준열,조재오 대한구강악안면병리학회 2011 대한구강악안면병리학회지 Vol.35 No.3

Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cancers. Recent data suggest that chemokines could be essential players in carcinogenesis and that tumor cells express chemokine receptors and use chemokines to metastasize to the target organ in many malignancies in humans. The aim of this study was to test the hypothesis that expression of SNPs in chemokine, CXCL1 and CXCL2 correlates with oral squamous cell carcinomas in Korean population. The CXCL1 and CXCL2 genotypes were determined in 21 subjects with oral squamous cell carcinoma and 90 control subjects without oral squamous cell carcinoma. The genotypes were determined by direct sequencing. The genotype distribution and allele frequency within the OSCC patients were not significantly different from those of control subjects. But among OSCC subjects, there was significant difference of CXCL1 gene in the degree of nuclear aberration. These findings suggest that CXCL1 -442C/T polymorphism and CXCL2 -264T/C polymorphism are not related to the development of OSCC but polymorphism of CXCL1 gene might have a relation with progression of OSCC in Korean population.

15-Deoxy-δ^^{12,14}-Prostaglandin J₂ Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

Kim, Jung-Hae,Kim, Hee-Sun 대한면역학회 2009 Immune Network Vol.9 No.2

15d-PGJ₂ has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-PGJ₂ on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-PGJ₂ on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-κB avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-PGJ₂ decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-PGJ₂ in SHR VSMCs was mediated through PPARγ, and dependent on NF-κB activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-PGJ₂ on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-PGJ₂ on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-PGJ₂/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-PGJ₂ on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPARγ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-PGJ₂/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

15-Deoxy-${\Delta}^{12,14}$-Prostaglandin $J_2$ Upregulates the Expression of LPS-Induced IL-8/CXCL8 mRNA in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

Kim, Jung-Hae,Kim, Hee-Sun The Korean Association of Immunobiologists 2009 Immune Network Vol.9 No.2

Background: 15d-$PGJ_2$ has been known to act as an anti-inflammatory agent and has anti-hypertensive effects. As a result of these properties, we examined the effect of 15d-$PGJ_2$ on the LPS-induced IL-8/CXCL8 mRNA expression in VSMCs from SHR. Methods: Effect and action mechanism of 15d-$PGJ_2$ on the expression of LPS-induced IL-8/CXCL8 mRNA in VSMCs from SHR and WKY were examined by using real-time polymerase chain reaction, electrophoretic mobility shift assay for NF-${\kappa}B$ avtivity, Western blotting analysis for ERK and p38 phosphorylation and flow cytometry for NAD(P)H oxidase activity. Results: 15d-$PGJ_2$ decreased the expression of LPS-induced IL-8/CXCL8 mRNA in WKY VSMCs, but increased the expression of LPS-induced IL-8/CXCL8 mRNA in SHR VSMCs. The upregulatory effect of 15d-$PGJ_2$ in SHR VSMCs was mediated through PPAR${\gamma}$, and dependent on NF-${\kappa}B$ activation and ERK phosphorylation. However, inhibition of the p38 signaling pathway augmented the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 mRNA. A NAD(P)H oxidase inhibitor inhibited the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 mRNA expression in SHR VSMCs, and an increase in NAD(P)H oxidase activity was detected in SHR VSMCs treated with 15d-$PGJ_2$/LPS. Conclusion: Our results indicate that the upregulatory effect of 15d-$PGJ_2$ on LPS-induced IL-8/CXCL8 expression in SHR VSMCs is mediated through the PPAR${\gamma}$ and ERK pathway, and may be related to NAD(P)H oxidase activity. However, p38 inactivation may also play an important role in 15d-$PGJ_2$/LPS-induced IL-8/CXCL8 expression in SHR VSMCs.

Intracellular Signaling Pathways that Regulate Macrophage Chemokine Expression in Response to Mycobacterium abscessus

Kim, Tae-Sung,Lee, Hye-Mi,Yoo, Hee-Kyung,Park, Young-Kil,Jo, Eun-Kyeong The Korean Society for Microbiology 2012 Journal of Bacteriology and Virology Vol.42 No.2

Mycobacterium abscessus (Mabc) is an emerging human pathogen. Less is known about the host immune response to Mabc than to M. tuberculosis. Here, we examined the intracellular signaling pathways that govern the expression of chemokines including (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 2 (CXCL2) in macrophages after infection with Mabc. Specifically, Mabc triggered the generation of reactive oxygen species (ROS) and the production of CCL2 and CXCL2 in murine bone marrow-derived macrophages (BMDMs). Mabc-induced CCL2, but not CXCL2, was dependent on the generation of ROS. Toll-like receptor (TLR) 2, MyD88, but not TRIF, was required for Mabc-induced CCL2 and CXCL2 expression. Additionally, Mabc infection significantly induced nuclear factor (NF)-${\kappa}B$ nuclear translocation and luciferase activity. The activation of NF-${\kappa}B$ was required for Mabc-induced CCL2, but not CXCL2 expression. Moreover, Mabc-induced ROS generation was required for NF-${\kappa}B$ activation. Treatment of BMDMs with Mabc rapidly induced the activation of mitogen-activated protein kinase (MAPKs) pathways. Interestingly, CCL2 expression was dependent on the activation of JNK and ERK1/2 pathways, whereas it was negatively regulated by the p38 MAPK pathway. In contrast, Mabc-dependent CXCL2 expression was not regulated by MAPK pathways. These data suggest that intracellular ROS generation is required for innate and inflammatory responses during Mabc infection of macrophages.

A systemic study on the vulnerability and fatality of prostate cancer patients towards COVID-19 through analysis of the TMPRSS2, CXCL10 and their co-expressed genes

Raza, Md. Thosif,Mizan, Shagufta Korea Genome Organization 2022 Genomics & informatics Vol.20 No.3

A pandemic of respiratory disease named coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is reported prostate cancer patients are susceptible to COVID-19 infection. To understand the possible causes of prostate cancer patients' increased vulnerability and mortality from COVID-19 infection, we focused on the two most important agents, transmembrane protease serine subtype 2 (TMPRSS2) and the C-X-C motif 10 (CXCL10). When SARS-CoV-2 binds to the host cell via S protein-angiotensin-converting enzyme-2 receptor interaction, TMPRSS2 contributes in the proteolytic cleavage of the S protein, allowing the viral and cellular membranes to fuse. CXCL10 is a cytokine found in elevated level in both COVID-19 and cancer-causing cytokine storm. We discovered that TMPRSS2 and CXCL10 are overexpressed in prostate cancer and COVID-19 using the UALCAN and GEPIA2 datasets. The functional importance of TMPRSS2 and CXCL10 in prostate cancer development was then determined by analyzing the frequency of genetic changes in their amino acid sequences using the cBioPortal online portal. Finally, we used the PANTHER database to examine the pathology of the targeted genes. We observed that TMPRSS2 and CXCL10, together with their often co-expressed genes, are important in the binding activity and immune responses in prostate cancer and COVID-19 infection, respectively. Finally, we found that TMPRSS2 and CXCL10 are two putative biomarkers responsible for the increased vulnerability and fatality of prostate cancer patients to COVID-19.

Overexpression of CXCL2 inhibits cell proliferation and promotes apoptosis in hepatocellular carcinoma

( Jun Ding ),( Kangdi Xu ),( Jie Zhang ),( Bingyi Lin ),( Yubo Wang ),( Shengyong Yin ),( Haiyang Xie ),( Lin Zhou ),( Shusen Zheng ) 생화학분자생물학회 2018 BMB Reports Vol.51 No.12

C-X-C motif chemokine ligand 2 (CXCL2) is a small secreted protein that exhibits a structure similar to the proangiogenic subgroup of the CXC chemokine family. Recently, accumulating evidence suggests that chemokines play a pivotal role in cancer progression and carcinogenesis. We examined the expression levels of 7 types of ELR+ CXCLs messenger RNA (mRNA) in 264 clinical samples. We found that CXCL2 expression was stably down-regulated in 94% of hepatocellular carcinoma (HCC) specimens compared with paired adjacent normal liver tissues and some HCC cell lines. Moreover, CXCL2 overexpression profoundly attenuated HCC cell proliferation and growth and induced apoptosis in vitro. In animal studies, we found that overexpressing CXCL2 by lentivirus also apparently inhibited the size and weight of subcutaneous tumours in nude mice. Furthermore, we demonstrated that CXCL2 induced HCC cell apoptosis via both nuclear and mitochondrial apoptosis pathways. Our results indicate that CXCL2 negatively regulates the cell cycle in HCC cells via the ERK1/2 signalling pathway. These results provide new insights into HCC and may ultimately lead to the discovery of innovative therapeutic approaches of HCC. [BMB Reports 2018; 51(12): 630-635]

Intracellular Signaling Pathways that Regulate Macrophage Chemokine Expression in Response to Mycobacterium abscessus

김태성,이혜미,유희경,박영길,조은경 대한미생물학회 2012 Journal of Bacteriology and Virology Vol.42 No.2

Mycobacterium abscessus (Mabc) is an emerging human pathogen. Less is known about the host immune response to Mabc than to M. tuberculosis. Here, we examined the intracellular signaling pathways that govern the expression of chemokines including (C-C motif) ligand 2 (CCL2) and (C-X-C motif) ligand 2 (CXCL2) in macrophages after infection with Mabc. Specifically, Mabc triggered the generation of reactive oxygen species (ROS) and the production of CCL2and CXCL2 in murine bone marrow-derived macrophages (BMDMs). Mabc-induced CCL2, but not CXCL2, was dependent on the generation of ROS. Toll-like receptor (TLR) 2, MyD88, but not TRIF, was required for Mabc-induced CCL2 and CXCL2 expression. Additionally, Mabc infection significantly induced nuclear factor (NF)-κB nuclear translocation and luciferase activity. The activation of NF-κB was required for Mabc-induced CCL2, but not CXCL2expression. Moreover, Mabc-induced ROS generation was required for NF-κB activation. Treatment of BMDMs with Mabc rapidly induced the activation of mitogen-activated protein kinase (MAPKs) pathways. Interestingly, CCL2expression was dependent on the activation of JNK and ERK1/2 pathways, whereas it was negatively regulated by the p38 MAPK pathway. In contrast, Mabc-dependent CXCL2 expression was not regulated by MAPK pathways. These data suggest that intracellular ROS generation is required for innate and inflammatory responses during Mabc infection of macrophages.

고혈압 쥐와 정상혈압 쥐의 혈관 평활근 세포에서 케모카인 발현 비교

김정혜 ( Jung Hae Kim ),박소영 ( So Young Park ),김희선 ( Hee Sun Kim ) 영남대학교 기초/임상의학연구소 2007 Yeungnam University Journal of Medicine Vol.24 No.2S

Background:The action of chemokines to the vascular inflammation plays a pathogenic role in the development and maintenance of hypertension. 1) Materials and methods:In the present study, the expression of chemokine IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 was investigated in cultured vascular smooth muscle cells (VSMC) obtained from the thoracic aorta of normotensive Wister-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR). We used real-time PCR and western blotting. Result:The expressions of IL-8/CXCL8, and MCP-1/CCL2 mRNA were stronger in VSMC from SHR than in WKY. However, the expression of RANTES/CCL5 was stronger in VSMC from WKY than in SHR. Expressions of CXCR1, CCR2, CD14 and PPARγ mRNA were stronger in VSMC from WKY than in SHR. Expressions of LPS-induced IL-8/CXCL8 and MCP-1/CCL2 mRNA were stronger in VSMC from SHR, but expression of LPS-induced RANTES/CCL5 was stronger in VSMC from WKY. A PPAR-γ ligand, 15-deoxy-Δ12, 14- prostaglandin J2 (15d-PGJ2) which possesses anti-inflammatory activity suppressed the expressions of LPS-induced IL-8/CXCL8, MCP-1/CCL2 and RANTES/CCL5 in VSMC from WKY and the expressions of LPS-induced MCP-1/CCL2 and RANTES/CCL5 expressions in SHR. But, the expression of LPS-induced IL-8/CXCL8 mRNA in SHR was increased by 15d- PGJ2. Angiotensin II (AngII) also induced IL-8/CXCL8 and MCP-1/CCL2 mRNA expressions in VSMC from SHR, but inhibited the expression of RANTES/CCL5 mRNA. Activities of LPS, or AngII-induced MAP kinases were stronger in VSMC from SHR than in WKY. Expression of AngII-induced IL-8/CXCL8 mRNA was associated with ERK phathway, and the expression of AngII-induced MCP-1/CCL2 mRNA was associated with p38 pathway, and the inhibition of RANTES/CCL5 mRNA by AngII was not associated with MAP Kinases pathways. Conclusion:Chemokine IL-8/CXCL8 and MCP-1/CCL2, not RANTES/CCL5, has a possibility to play a critical role in the pathogenesis of hypertension in the SHR.

CXCL1 and CXCL2 Polymorphisms of Oral Squamous Cell Carcinoma in Korean

강상욱,김준열,조재오 대한구강악안면병리학회 2011 대한구강악안면병리학회지 Vol.35 No.3

Oral squamous cell carcinoma (OSCC) is the most common cancer of oral cancers. Recent data suggest that chemokines could be essential players in carcinogenesis and that tumor cells express chemokine receptors and use chemokines to metastasize to the target organ in many malignancies in humans. The aim of this study was to test the hypothesis that expression of SNPs in chemokine, CXCL1 and CXCL2 correlates with oral squamous cell carcinomas in Korean population. The CXCL1 and CXCL2 genotypes were determined in 21 subjects with oral squamous cell carcinoma and 90 control subjects without oral squamous cell carcinoma. The genotypes were determined by direct sequencing. The genotype distribution and allele frequency within the OSCC patients were not significantly different from those of control subjects. But among OSCC subjects, there was significant difference of CXCL1 gene in the degree of nuclear aberration. These findings suggest that CXCL1 -442C/T polymorphism and CXCL2 -264T/C polymorphism are not related to the development of OSCC but polymorphism of CXCL1 gene might have a relation with progression of OSCC in Korean population.