Honokiol possesses potential anti-inflammatory effects on rheumatoid arthritis and GM-CSF can be a target for its treatment.
OBJECTIVE
To observe the anti-inflammatory effects of honokiol in primary cultures of peripheral blood mononuclear cells of rheumatoid arthritis patients, the pro-inflammatory cytokines and potential targets were investigated.


METHODS
The levels of GM-CSF, IL-1β, TNF-α and IL-8 were determined by ELISA assay. The genes and proteins expression were analyzed by real-time PCR and Western blotting respectively.


RESULTS
The serum IL-1β, TNF-α and GM-CSF levels were 1.76-, 2.16- and 3.57-fold increased in patients with RA as compared to those of control group. Honokiol inhibited the expression levels of IL-1β, TNF-α, GM-CSF and IL-8 in PBMCs with a dose-dependent manner. Measurements obtained from supernatants were positively correlated between TNF-α and IL-1β, moreover, similar results found TNF-α levels positively correlated with GM-CSF and IL-8 activity in the supernatants of PBMCs isolated from RA patients. Furthermore, the mRNA and protein expression of IL-1β, GM-CSF and IL-8 were up-regulated when the PBMCs exposure to TNF-α, however, honokiol treatment significantly reversed the expression of IL-1β, TNF-α and GM-CSF in response to TNF-α with a dose-dependent manner.


CONCLUSIONS
This study demonstrates that honokiol could possess potential anti-inflammatory effects and inhibits TNF-α-induced IL-1β, GM-CSF and IL-8 production in PBMCs from rheumatoid arthritis patients.
Department of Immunology and Rheumatology, Affiliated Hospital of Weifang Medical University Weifang 261031, Shandong, China.
Xiao-Dong
XD
Wang
Department of Immunology and Rheumatology, Affiliated Hospital of Weifang Medical University Weifang 261031, Shandong, China.
Ying-Liang
YL
Wang
Department of Immunology and Rheumatology, Clinical Faculty (Affiliated Hospital), Weifang Medical University Weifang 261053, Shandong, China.
Wen-Feng
WF
Gao
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D000498:Allyl Compounds; D010636:Phenols
D000893:Anti-Inflammatory Agents; D018501:Antirheumatic Agents; D001713:Biphenyl Compounds; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D017705:Lignans; D014409:Tumor Necrosis Factor-alpha; C508606:CXCL8 protein, human; C508585:IL1B protein, human; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
GM-CSF; IL-1β; IL-8; Rheumatoid arthritis; TNF-α