Dynamics of proinflammatory and anti-inflammatory cytokines in blood plasma in the treatment of back pain with non-steroidal anti-inflammatory drugs

Maslova, I. G.; Слободін, Т.М.; Mykhailovska, N. S.; Lisyanyi, Nikolay

doi:10.15587/2519-4798.2019.185451

Cited by 2 publications

(4 citation statements)

References 8 publications

(12 reference statements)

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“…We further evaluated whether there was a correlation between the pathological to protective tRAS axis gene expressions (AGTR1/AGTR2, AGTR1/MAS1) and inflammatory to anti-inflammatory gene expression markers (Il-6/IL-10, 1L-8/IL-10, and TNF-α/IL-10) in this experimental setting. Ratios of pro-inflammatory to anti-inflammatory markers (IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10) are indicators of the inflammatory state of the IVD and low back pain [ 38 , 39 ]. Our results revealed that AGTR1/AGTR2 and AGTR1/MAS1 gene expression ratios were significantly correlated with the pro-inflammatory/anti-inflammatory marker ratios Il-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 ( Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

“… Illustration of tRAS axis ratios (AGTR1/AGTR2, AGTR1/MAS1) [ 11 ] and inflammatory to anti-inflammatory gene expression markers (Il-6/IL-10, IL-8/IL-10, and TNF-α/IL-10) after 24 h ( A ) and 48 h ( B ) of drug or control exposure. Ratios of pro-inflammatory to anti-inflammatory markers are indicators for the inflammatory state of the intervertebral disc and low back pain [ 38 , 39 ]. AGTR1/AGTR2 and AGTR1/MAS1 gene expression ratios were positively correlated with the pro-inflammatory/anti-inflammatory marker ratios Il-6/IL-10, IL-8/IL-10, and TNF-α/IL-10.…”

Section: Figurementioning

confidence: 99%

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In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells

Saravi

Basoli

et al. 2022

Cells

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Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from four human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter, the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 h of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Furthermore, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated by utilizing Western blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease.

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Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells

Saravi

Basoli

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…this experimental setting. Ratios of pro-inflammatory to anti-inflammatory markers (IL-6/IL-10, IL-8/IL-10, and TNF-α/IL-10) are indicators of the inflammatory state of the IVD and low back pain [27,28]. Our results revealed that AGTR1/AGTR2 and AGTR1/MAS1 gene expression ratios were significantly correlated with the pro-inflammatory/anti-inflammatory marker ratios Il-6/IL-10, IL-8/IL-10, and TNF-α/IL-10 (Figure 3).…”

Section: Gene Expression Analysismentioning

confidence: 99%

“…Illustration of tRAS axis ratios (AGTR1/AGTR2, AGTR1/MAS1) [11] and inflammatory to anti-inflammatory gene expression markers (Il-6/IL-10, IL-8/IL-10, and TNF-a/IL-10) after 24h (A) and 48h (B) of drug or control exposure. Ratios of pro-inflammatory to anti-inflammatory markers are indicators for the inflammatory state of the intervertebral disc and low back pain [27,28]. AGTR1/AGTR2 and AGTR1/MAS1 gene expression ratios were positively correlated with the proinflammatory/anti-inflammatory marker ratios Il-6/IL-10, IL-8/IL-10, and TNF-a/IL-10.…”

Section: Figurementioning

confidence: 99%

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells

Saravi¹,

Li²,

Basoli³

et al. 2022

Preprint

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Low back pain is a clinically highly relevant musculoskeletal burden and is associated with inflammatory as well as degenerative processes of the intervertebral disc. However, the pathophysiology and cellular pathways contributing to this devastating condition are still poorly understood. Based on previous evidence, we hypothesize that tissue renin-angiotensin system (tRAS) components, including the SARS-CoV-2 entry receptor angiotensin-converting enzyme 2 (ACE2), are present in human nucleus pulposus (NP) cells and associated with inflammatory and degenerative processes. Experiments were performed with NP cells from 4 human donors. The existence of angiotensin II, angiotensin II type 1 receptor (AGTR1), AGTR2, MAS-receptor (MasR), and ACE2 in human NP cells was validated with immunofluorescent staining and gene expression analysis. Hereafter the cell viability was assessed after adding agonists and antagonists of the target receptors as well as angiotensin II in different concentrations for up to 48 hours of exposure. A TNF-α-induced inflammatory in vitro model was employed to assess the impact of angiotensin II addition and the stimulation or inhibition of the tRAS receptors on inflammation, tissue remodeling, expression of tRAS markers, and the release of nitric oxide (NO) into the medium. Further, protein levels of IL-6, IL-8, IL-10, and intracellular as well as secreted angiotensin II were assessed after exposing the cells to the substances, and inducible nitric oxide synthase (iNOS) levels were evaluated utilizing Western Blot. The existence of tRAS receptors and angiotensin II were validated in human NP cells. Cell viability analysis revealed no cytotoxic effects of angiotensin II. The AGTR1 inhibitor Candesartan and the MAS receptors AVE0991 showed cytotoxic effects at high concentrations (100 µM). The addition of angiotensin II only showed a mild impact on gene expression markers. However, there was a significant increase in NO secreted by the cells. The gene expression ratios of pro-inflammatory/anti-inflammatory cytokines IL-6/IL--10, IL-8/IL-10, and TNF-α /IL-10 were positively correlated with the AGTR1/AGTR2 and AGTR1/MAS1 ratios, respectively. The stimulation of the AGTR2 MAS-receptor and the inhibition of the AGTR1 receptor revealed beneficial effects on the gene expression of inflammatory and tissue remodeling markers. This finding was also present at the protein level. We did not find alterations in iNOS protein concentrations after adding the drugs. The current data showed that tRAS components are expressed in human NP cells and are associated with inflammatory and degenerative processes. Further characterization of the associated pathways is warranted. The findings indicate that tRAS modulation might be a novel therapeutic approach to intervertebral disc disease.

show abstract

Dynamics of proinflammatory and anti-inflammatory cytokines in blood plasma in the treatment of back pain with non-steroidal anti-inflammatory drugs

Cited by 2 publications

References 8 publications

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells

In Vitro Characterization of a Tissue Renin-Angiotensin System in Human Nucleus Pulposus Cells

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