A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients
© 2022. The Author(s)..
BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease that mostly affects different joints of the body. Macrophages are the predominant cells that mediate disease progression by secreting several pro-inflammatory mediators. Different receptors are involved in macrophages' function including the adenosine receptors (AR). Our main objective in this study was to assess the effect of applying A2A adenosine receptor agonist (CGS-21,680) on the gene expression of inflammatory mediators including bone morphogenetic proteins (BMP)-2, 4 and matrix metalloproteinases (MMP)-3, 8, 9, and 13 on the macrophages from AS patients compared to healthy macrophages.
METHODS: Monocytes were isolated from the whole blood of 28 individuals (AS patients and healthy controls in a 1:1 ratio). Macrophages were differentiated using macrophage colony-stimulating factor (M-CSF), and flow cytometry was performed to confirm surface markers. CGS-21,680 was used to treat cells that had been differentiated. Using SYBR green real-time PCR, relative gene expression was determined.
RESULTS: Activating A2AAR diminished MMP8 expression in healthy macrophages while it cannot reduce MMP8 expression in patients' macrophages. The effect of A2AAR activation on the expression of BMP2 and MMP9 reached statistical significance neither in healthy macrophages nor in the patients' group. We also discovered a significant positive connection between MMP8 expression and patient scores on the Bath ankylosing spondylitis functional index (BASFI).
CONCLUSION: Due to the disability of A2AAR activation in the reduction of MMP8 expression in patients' macrophages and the correlation of MMP8 expression with BASFI index in patients, these results represent defects and dysregulations in the related signaling pathway in patients' macrophages.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
|---|---|
| Enthalten in: |
BMC musculoskeletal disorders - 23(2022), 1 vom: 12. Okt., Seite 908 |
| Sprache: |
Englisch |
|---|
| Weiterer Titel: |
Authors and affiliations |
|---|
| Beteiligte Personen: |
Sadatpour, Omid [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 13.10.2022 Date Revised 15.10.2022 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s12891-022-05846-0 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM347363024 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM347363024 | ||
| 003 | DE-627 | ||
| 005 | 20231226033637.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s12891-022-05846-0 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1157.xml |
| 035 | |a (DE-627)NLM347363024 | ||
| 035 | |a (NLM)36221125 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Sadatpour, Omid |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a A2A adenosine receptor agonist reduced MMP8 expression in healthy M2-like macrophages but not in macrophages from ankylosing spondylitis patients |
| 246 | 3 | 3 | |a Authors and affiliations |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 13.10.2022 | ||
| 500 | |a Date Revised 15.10.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022. The Author(s). | ||
| 520 | |a BACKGROUND: Ankylosing spondylitis (AS) is an inflammatory autoimmune disease that mostly affects different joints of the body. Macrophages are the predominant cells that mediate disease progression by secreting several pro-inflammatory mediators. Different receptors are involved in macrophages' function including the adenosine receptors (AR). Our main objective in this study was to assess the effect of applying A2A adenosine receptor agonist (CGS-21,680) on the gene expression of inflammatory mediators including bone morphogenetic proteins (BMP)-2, 4 and matrix metalloproteinases (MMP)-3, 8, 9, and 13 on the macrophages from AS patients compared to healthy macrophages | ||
| 520 | |a METHODS: Monocytes were isolated from the whole blood of 28 individuals (AS patients and healthy controls in a 1:1 ratio). Macrophages were differentiated using macrophage colony-stimulating factor (M-CSF), and flow cytometry was performed to confirm surface markers. CGS-21,680 was used to treat cells that had been differentiated. Using SYBR green real-time PCR, relative gene expression was determined | ||
| 520 | |a RESULTS: Activating A2AAR diminished MMP8 expression in healthy macrophages while it cannot reduce MMP8 expression in patients' macrophages. The effect of A2AAR activation on the expression of BMP2 and MMP9 reached statistical significance neither in healthy macrophages nor in the patients' group. We also discovered a significant positive connection between MMP8 expression and patient scores on the Bath ankylosing spondylitis functional index (BASFI) | ||
| 520 | |a CONCLUSION: Due to the disability of A2AAR activation in the reduction of MMP8 expression in patients' macrophages and the correlation of MMP8 expression with BASFI index in patients, these results represent defects and dysregulations in the related signaling pathway in patients' macrophages | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Adenosine A2A receptor | |
| 650 | 4 | |a Ankylosing spondylitis | |
| 650 | 4 | |a Bone morphogenetic protein | |
| 650 | 4 | |a Macrophages | |
| 650 | 4 | |a Matrix metalloproteinase | |
| 650 | 7 | |a Bone Morphogenetic Proteins |2 NLM | |
| 650 | 7 | |a Inflammation Mediators |2 NLM | |
| 650 | 7 | |a Purinergic P1 Receptor Agonists |2 NLM | |
| 650 | 7 | |a Receptors, Purinergic P1 |2 NLM | |
| 650 | 7 | |a Macrophage Colony-Stimulating Factor |2 NLM | |
| 650 | 7 | |a 81627-83-0 |2 NLM | |
| 650 | 7 | |a MMP8 protein, human |2 NLM | |
| 650 | 7 | |a EC 3.4.24.34 |2 NLM | |
| 650 | 7 | |a Matrix Metalloproteinase 8 |2 NLM | |
| 650 | 7 | |a EC 3.4.24.34 |2 NLM | |
| 650 | 7 | |a Matrix Metalloproteinase 9 |2 NLM | |
| 650 | 7 | |a EC 3.4.24.35 |2 NLM | |
| 700 | 1 | |a Ebrahimi, Mohammad Taha |e verfasserin |4 aut | |
| 700 | 1 | |a Akhtari, Maryam |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmadzadeh, Nooshin |e verfasserin |4 aut | |
| 700 | 1 | |a Vojdanian, Mahdi |e verfasserin |4 aut | |
| 700 | 1 | |a Jamshidi, Ahmadreza |e verfasserin |4 aut | |
| 700 | 1 | |a Farhadi, Elham |e verfasserin |4 aut | |
| 700 | 1 | |a Mahmoudi, Mahdi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t BMC musculoskeletal disorders |d 2000 |g 23(2022), 1 vom: 12. Okt., Seite 908 |w (DE-627)NLM111431875 |x 1471-2474 |7 nnns |
| 773 | 1 | 8 | |g volume:23 |g year:2022 |g number:1 |g day:12 |g month:10 |g pages:908 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s12891-022-05846-0 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 23 |j 2022 |e 1 |b 12 |c 10 |h 908 | ||