PMID- 35625855
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230916
IS  - 2227-9059 (Print)
IS  - 2227-9059 (Electronic)
IS  - 2227-9059 (Linking)
VI  - 10
IP  - 5
DP  - 2022 May 11
TI  - Impact of Delta(9)-Tetrahydrocannabinol on Rheumatoid Arthritis Synovial Fibroblasts 
      Alone and in Co-Culture with Peripheral Blood Mononuclear Cells.
LID - 10.3390/biomedicines10051118 [doi]
LID - 1118
AB  - delta9-Tetrahydrocannabinol (THC) has demonstrated anti-inflammatory effects in 
      animal models of arthritis, but its mechanism of action and cellular targets are 
      still unclear. The purpose of this study is to elucidate the effects of THC 
      (0.1-25 microM) on synovial fibroblasts from patients with rheumatoid arthritis 
      (RASF) and peripheral blood mononuclear cells (PBMC) from healthy donors in 
      respect to proliferation, calcium mobilization, drug uptake, cytokine and 
      immunoglobulin production. Intracellular calcium and drug uptake were determined 
      by fluorescent dyes Cal-520 and PoPo3, respectively. Cytokine and immunoglobulin 
      production were evaluated by ELISA. Cannabinoid receptors 1 and 2 (CB(1) and 
      CB(2)) were detected by flow cytometry. RASF express CB(1) and CB(2) and the 
      latter was increased by tumor necrosis factor (TNF). In RASF, THC (>/=5 microM) 
      increased intracellular calcium levels/PoPo3 uptake in a TRPA1-dependent manner 
      and reduced interleukin-8 (IL-8) and matrix metalloprotease 3 (MMP-3) production 
      at high concentrations (25 microM). Proliferation was slightly enhanced at 
      intermediate THC concentrations (1-10 microM) but was completely abrogated at 25 microM. 
      In PBMC alone, THC decreased interleukin-10 (IL-10) production and increased 
      immunoglobulin G (IgG). In PBMC/RASF co-culture, THC decreased TNF production 
      when cells were stimulated with interferon-gamma (IFN-gamma) or CpG. THC provides pro- 
      and anti-inflammatory effects in RASF and PBMC. This is dependent on the 
      activating stimulus and concentration of THC. Therefore, THC might be used to 
      treat inflammation in RA but it might need titrating to determine the effective 
      concentration.
FAU - Lowin, Torsten
AU  - Lowin T
AUID- ORCID: 0000-0001-7368-2776
AD  - Poliklinik, Funktionsbereich & Hiller Forschungszentrum fur Rheumatologie, 
      University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
FAU - Kok, Christina
AU  - Kok C
AD  - Poliklinik, Funktionsbereich & Hiller Forschungszentrum fur Rheumatologie, 
      University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
FAU - Smutny, Sophie
AU  - Smutny S
AD  - Poliklinik, Funktionsbereich & Hiller Forschungszentrum fur Rheumatologie, 
      University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
FAU - Pongratz, Georg
AU  - Pongratz G
AD  - Poliklinik, Funktionsbereich & Hiller Forschungszentrum fur Rheumatologie, 
      University Hospital Duesseldorf, 40225 Duesseldorf, Germany.
LA  - eng
PT  - Journal Article
DEP - 20220511
PL  - Switzerland
TA  - Biomedicines
JT  - Biomedicines
JID - 101691304
PMC - PMC9138512
OTO - NOTNLM
OT  - PBMC
OT  - TRPA1
OT  - calcium
OT  - cannabinoid receptors
OT  - cannabis
OT  - cytokines
OT  - rheumatoid arthritis
OT  - synovial fibroblast
OT  - tetrahydrocannabinol
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2022/05/29 06:00
MHDA- 2022/05/29 06:01
PMCR- 2022/05/11
CRDT- 2022/05/28 01:08
PHST- 2022/04/08 00:00 [received]
PHST- 2022/05/06 00:00 [revised]
PHST- 2022/05/09 00:00 [accepted]
PHST- 2022/05/28 01:08 [entrez]
PHST- 2022/05/29 06:00 [pubmed]
PHST- 2022/05/29 06:01 [medline]
PHST- 2022/05/11 00:00 [pmc-release]
AID - biomedicines10051118 [pii]
AID - biomedicines-10-01118 [pii]
AID - 10.3390/biomedicines10051118 [doi]
PST - epublish
SO  - Biomedicines. 2022 May 11;10(5):1118. doi: 10.3390/biomedicines10051118.