Plectranthus amboinicus Attenuates Inflammatory Bone Erosion in Mice with Collagen-induced Arthritis by Downregulation of RANKL-induced NFATc1 Expression

2011 ◽  
Vol 38 (9) ◽  
pp. 1844-1857 ◽  
Author(s):  
YU-CHIEH HSU ◽  
CHIA-PI CHENG ◽  
DEH-MING CHANG
Keyword(s):  
Animal Model ◽  
Rosmarinic Acid ◽  
Nuclear Translocation ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Collagen Induced Arthritis ◽  
Activated T Cells ◽  
Plectranthus Amboinicus

Objective.Plectranthus amboinicus has been known to treat inflammatory diseases or swelling symptoms. We investigated whether P. amboinicus exhibited an inhibitory effect on osteoclastogenesis in vitro and inflammatory bone erosion in collagen-induced arthritis (CIA) mice, an animal model of rheumatoid arthritis. We attempted to identify the active component of P. amboinicus involved in regulation of osteoclastogenesis.Methods.We treated M-CSF- and RANKL-stimulated murine bone marrow-derived macrophages (BMM) and RANKL-induced RAW264.7 cells with different concentrations of P. amboinicus or rosmarinic acid, a phytopolyphenol purified from P. amboinicus, to monitor osteoclast formation by TRAP staining. The mechanism of the inhibition was studied by biochemical analysis such as RT-PCR and immunoblotting. CIA mice were administered gavages of P. amboinicus (375 mg/kg) or placebo. Then clinical, histological, and biochemical measures were assessed to determine the effects of P. amboinicus on synovial inflammation and bone erosion by H&E staining of the inflamed joints and ELISA.Results.Rosmarinic acid strongly inhibited RANKL-induced NF-κB activation and nuclear factor of activated T cells c1 (NFATc1) nuclear translocation in BMM, and also inhibited RANKL-induced formation of TRAP-positive multinucleated cells. A pit formation assay and the CIA animal model showed that P. amboinicus significantly inhibited the bone-resorbing activity of mature osteoclasts.Conclusion.We postulated that rosmarinic acid conferred the inhibitory activity on P. amboinicus for inhibition of osteoclastogenesis via downregulation of RANKL-induced NFATc1 expression. Our results indicated the possibility of P. amboinicus as a new remedy against inflammatory bone destruction.

scholarly journals Targeting of Phospholipase D1 Ameliorates Collagen-Induced Arthritis via Modulation of Treg and Th17 Cell Imbalance and Suppression of Osteoclastogenesis

2020 ◽  
Vol 21 (9) ◽  
pp. 3230
Author(s):  
Hyun Jung Yoo ◽  
Won Chan Hwang ◽  
Do Sik Min
Keyword(s):  
Autoimmune Diseases ◽  
Cell Population ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Bone Erosion ◽  
Bone Destruction ◽  
Systemic Autoimmune Disease ◽  
Collagen Induced Arthritis ◽  
Phospholipase D1

Phospholipase D1 (PLD1) plays a crucial role in various inflammatory and autoimmune diseases. Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease. However, the role of PLD1 in the pathogenesis of RA remains unknown. Here, we first investigated the role and effects of PLD1 in collagen-induced arthritis (CIA) and found that genetic and pharmacological inhibition of PLD1 in DBA1/J mice with CIA reduced the incidence of CIA, decreased the clinical score, and abrogated disease symptoms including infiltration of leukocytes, synovial inflammation, bone erosion, and cartilage destruction. Moreover, ablation and inhibition of PLD1 suppressed the production of type II collagen-specific IgG2a autoantibody and proinflammatory cytokines, accompanied by an increase in the regulatory T (Treg) cell population and a decrease in the Th17 cell population in CIA mice. The PLD1 inhibitor also promoted differentiation of Treg cells and suppressed differentiation of Th17 cells in vitro. Furthermore, the PLD1 inhibitor attenuated pathologic bone destruction in CIA mice by suppressing osteoclastogenesis and bone resorption. Thus, our findings indicate that the targeting of PLD1 can ameliorate CIA by modulating the imbalance of Treg and Th17 cells and suppressing osteoclastogenesis, which might be a novel strategy to treat autoimmune diseases, such as RA.

scholarly journals IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

2020 ◽  
Vol 21 (3) ◽  
pp. 1130 ◽  
Author(s):  
Fumitoshi Ohori ◽  
Hideki Kitaura ◽  
Saika Ogawa ◽  
Wei-Ren Shen ◽  
Jiawei Qi ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Nuclear Translocation ◽  
Bone Marrow Cells ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Ct Reconstruction ◽  
Tnf Α

Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption.

scholarly journals 3-Hydroxyolean-12-en-27-oic Acids Inhibit RANKL-Induced Osteoclastogenesis in Vitro and Inflammation-Induced Bone Loss in Vivo

2020 ◽  
Vol 21 (15) ◽  
pp. 5240
Author(s):  
Wonyoung Seo ◽  
Suhyun Lee ◽  
Phuong Thao Tran ◽  
Thi Quynh-Mai Ngo ◽  
Okwha Kim ◽  
...  
Keyword(s):  
Bone Destruction ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Marker Genes ◽  
Tartrate Resistant Acid Phosphatase ◽  
Specific Marker ◽  
Nuclear Factor ◽  
Activated T Cells

Olean-12-en-27-oic acids possess a variety of pharmacological effects. However, their effects and underlying mechanisms on osteoclastogenesis remain unclear. This study aimed to investigate the anti-osteoclastogenic effects of five olean-12-en-27-oic acid derivatives including 3α,23-isopropylidenedioxyolean-12-en-27-oic acid (AR-1), 3-oxoolean-12-en-27-oic acid (AR-2), 3α-hydroxyolean-12-en-27-oic acid (AR-3), 23-hydroxy-3-oxoolean-12-en-27-oic acid (AR-4), and aceriphyllic acid A (AR-5). Among the five olean-12-en-27-oic acid derivatives, 3-hydroxyolean-12-en-27-oic acid derivatives, AR-3 and AR-5, significantly inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced mature osteoclast formation by reducing the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, F–actin ring formation, and mineral resorption activity. AR-3 and AR-5 decreased RANKL-induced expression levels of osteoclast-specific marker genes such as c-Src, TRAP, and cathepsin K (CtsK) as well as c-Fos and nuclear factor of activated T cells cytoplasmic 1 (NFATc1). Mice treated with either AR-3 or AR-5 showed significant protection of the mice from lipopolysaccharide (LPS)-induced bone destruction and osteoclast formation. In particular, AR-5 suppressed RANKL-induced phosphorylation of JNK and ERK mitogen-activated protein kinases (MAPKs). The results suggest that AR-3 and AR-5 attenuate osteoclast formation in vitro and in vivo by suppressing RANKL-mediated MAPKs and NFATc1 signaling pathways and could potentially be lead compounds for the prevention or treatment of osteolytic bone diseases.

Polymorphonuclear Neutrophils in Osteomyelitis: Link to Osteoclast Generation and Bone Resorption

2012 ◽  
Vol 10 (3) ◽  
pp. 413-426 ◽  
Author(s):  
M.M. Gaida ◽  
B. Mayer ◽  
S. Stegmaier ◽  
P. Schirmacher ◽  
C. Wagner ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Bone Erosion ◽  
Ex Vivo ◽  
Bone Destruction ◽  
Cathepsin K ◽  
Class Ii ◽  
Osteoclast Formation ◽  
Polymorphonuclear Neutrophils ◽  
Tartrate Resistant Acid Phosphatase

Chronic and persistent inflammatory processes in bones may lead to severe erosions with consequent functional impairment sometimes requiring amputation of the limb. To explore the relationship between inflammation and bone erosion, biopsies of patients with osteomyelitis due to arterial occlusive disease or to diabetes mellitus were examined (n=31). Histologically, inflammation and bone erosion were confirmed. In the eroded bones the number of osteoclasts correlated with the abundance of infiltrated polymorphonuclear neutrophils (PMN), which were highly activated as shown by expression of MHC class II. For functional characterisation of the infiltrating PMN, patients with implant-associated osteomyelitis, a condition associated with persistent bacterial infection and bone destruction, were recruited. The cells were recovered from infected sites and examined ex vivo. These PMN expressed MHC class II and produced interleukin (IL)-8, a further indication of PMN activation. To assess a possible link between infiltrating PMN and bone erosion, we tested the effect of IL-8 on osteoclast generation in vitro. CD14+ monocytes derived from the peripheral blood of healthy individuals were cultivated with monocyte colony stimulating factor (M-CSF) and IL-8. Within 3 days, a translocation of the transcription factor NFATcl into the nucleus was seen, and by 10 to 20 days multinucleated cells with typical osteoclast morphology appeared that expressed tartrate-resistant acid phosphatase (TRAP) and cathepsin K. Moreover, the cells were able to resorb bone, proving that IL-8 was able to induce the differentiation of monocytes to osteoclasts. Because IL-8 is a major cytokine produced by activated PMN, we propose that in the course of persistent infection infiltrating PMN contribute to induction of osteoclast formation, thus providing a link between inflammation and bone erosion.

scholarly journals Immunological Reaction in TNF-α-Mediated Osteoclast Formation and Bone ResorptionIn VitroandIn Vivo

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hideki Kitaura ◽  
Keisuke Kimura ◽  
Masahiko Ishida ◽  
Haruka Kohara ◽  
Masako Yoshimatsu ◽  
...  
Keyword(s):  
T Cells ◽  
Bone Metabolism ◽  
Stromal Cells ◽  
Fas Ligand ◽  
Bone Marrow Cells ◽  
Bone Destruction ◽  
Osteoclast Formation ◽  
Bone Diseases

Tumor necrosis factor-α(TNF-α) is a cytokine produced by monocytes, macrophages, and T cells and is induced by pathogens, endotoxins, or related substances. TNF-αmay play a key role in bone metabolism and is important in inflammatory bone diseases such as rheumatoid arthritis. Cells directly involved in osteoclastogenesis include macrophages, which are osteoclast precursor cells, osteoblasts, or stromal cells. These cells express receptor activator of NF-κB ligand (RANKL) to induce osteoclastogenesis, and T cells, which secrete RANKL, promote osteoclastogenesis during inflammation. Elucidating the detailed effects of TNF-αon bone metabolism may enable the identification of therapeutic targets that can efficiently suppress bone destruction in inflammatory bone diseases. TNF-αis considered to act by directly increasing RANK expression in macrophages and by increasing RANKL in stromal cells. Inflammatory cytokines such as interleukin- (IL-) 12, IL-18, and interferon-γ(IFN-γ) strongly inhibit osteoclast formation. IL-12, IL-18, and IFN-γinduce apoptosis in bone marrow cells treated with TNF-α  in vitro, and osteoclastogenesis is inhibited by the interactions of TNF-α-induced Fas and Fas ligand induced by IL-12, IL-18, and IFN-γ. This review describes and discusses the role of cells concerned with osteoclast formation and immunological reactions in TNF-α-mediated osteoclastogenesisin vitroandin vivo.

scholarly journals Fucoidan Prevents RANKL-Stimulated Osteoclastogenesis and LPS-Induced Inflammatory Bone Loss via Regulation of Akt/GSK3β/PTEN/NFATc1 Signaling Pathway and Calcineurin Activity

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 345 ◽  
Author(s):  
Sheng-Hua Lu ◽  
Yi-Jan Hsia ◽  
Kuang-Chung Shih ◽  
Tz-Chong Chou
Keyword(s):  
Bone Loss ◽  
Molecular Mechanisms ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Calcineurin Activity

Excessive osteoclast differentiation and/or function plays a pivotal role in the pathogenesis of bone diseases such as osteoporosis and rheumatoid arthritis. Here, we examined whether fucoidan, a sulfated polysaccharide present in brown algae, attenuates receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and lipopolysaccharide (LPS)-induced bone resorption in vivo, and investigated the molecular mechanisms involved. Our results indicated that fucoidan significantly inhibited osteoclast differentiation in RANKL-stimulated macrophages and the bone resorbing activity of osteoclasts. The effects of fucoidan may be mediated by regulation of Akt/GSK3β/PTEN signaling and suppression of the increase in intracellular Ca2+ level and calcineurin activity, thereby inhibiting the translocation of nuclear factor-activated T cells c1 (NFATc1) into the nucleus. However, fucoidan-mediated NFATc1 inactivation was greatly reversed by kenpaullone, a GSK3β inhibitor. In addition, using microcomputer tomography (micro-CT) scanning and bone histomorphometry, we found that fucoidan treatment markedly prevented LPS-induced bone erosion in mice. Collectively, we demonstrated that fucoidan was capable of inhibiting osteoclast differentiation and inflammatory bone loss, which may be modulated by regulation of Akt/GSK3β/PTEN/NFATc1 and Ca2+/calcineurin signaling cascades. These findings suggest that fucoidan may be a potential agent for the treatment of osteoclast-related bone diseases.

scholarly journals Lemon Balm Extract and Its Major Chemical Compound, Rosmarinic Acid, Alleviate Damages of Liver in an Animal Model of Nonalcoholic Steatohepatitis (NASH) (P06-093-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Gyhye Yoo ◽  
Myungsuk Kim ◽  
Ahmad Randy ◽  
Yang-Ju Son ◽  
Chi Rak Hong ◽  
...  
Keyword(s):  
Animal Model ◽  
Chemical Compound ◽  
Rosmarinic Acid ◽  
Hepg2 Cells ◽  
In Vivo Model ◽  
World Population ◽  
Lemon Balm ◽  
Major Chemical

Abstract Objectives The non-alcoholic fatty liver disease (NAFLD) comprises the broad histopathological states of liver, that ranging from asymptomatic hepatic steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. In some studies, they suppose that almost 25–30% of world population is underlying NAFLD. Lemon balm (Melissa officinalis) is the herb that has some traditional medicinal usages. Also rosmarinic acid (RA; O-caffeoyl-3,4-dihydroxyphenyl lactic acid), the major chemical compound of lemon balm, already reported that it has the potency on anti-obesity and -inflammatory. Hence, we evaluate the whether lemon balm extract (LBE) and RA could suppress the pathogenesis of NASH using an in vitro and in vivo model. Methods In vitro model: The palmitic acid (PA) exposed HepG2 hepatocellular carcinoma cells can imitate the lipid accumulation in hepatocytes. PA exposed HepG2 cells were exposed with or without LBE or RA. In vivo model: The methionine- and choline-deficient (MCD) diet fed db/db C57BL/6 J mice model was used. This model is known as it can mimic well symptoms of human NAFLD. The LBE or RA were treated by oral gavage. Results With the MCD diet only, the severe liver damage was caused by progression of NASH in animal model. LBE and RA treatments alleviated the oxidative stress in the MCD diet-fed db/db mice and PA-exposed HepG2 cells by increasing the expression of antioxidant enzymes (NRF2, SOD) and augmented lipolysis-related gene (PPARα, PGC-1α, CPT-1 L) expression. In addition, LBE and RA treatments inhibited the expression of genes involved in hepatic fibrosis (α-SMA, COL1A1) and fatty acid synthesis (SREBP-1c, CPT-1 L) and activated AMP-activated protein kinase in vitro and in vivo. Also, the histopathological results were ameliorated by treatment of LBE or RA. Conclusions LBE and RA modulate lipid metabolism via AMPK activation and suppress inflammation via changes in NRF2 and NF-κB signalling. Importantly, the extract of lemon balm obtained with 20% EtOH showed effectiveness similar to that of RA at high concentrations. Therefore, LBE may be a good candidate for the treatment and prevention of NASH. Funding Sources This work was supported by the National Research Council of Science & Technology (NST) funded by the Korea Government (MSIP) (grant No. CRC-15-01-KIST). Supporting Tables, Images and/or Graphs

scholarly journals The Death Receptor 3–TNF-like protein 1A pathway drives adverse bone pathology in inflammatory arthritis

2008 ◽  
Vol 205 (11) ◽  
pp. 2457-2464 ◽  
Author(s):  
Melanie Jane Bull ◽  
Anwen Siân Williams ◽  
Zarabeth Mecklenburgh ◽  
Claudia Jane Calder ◽  
Jason Peter Twohig ◽  
...  
Keyword(s):  
Bone Erosion ◽  
Joint Destruction ◽  
Death Receptor ◽  
Bone Destruction ◽  
Chronic Inflammatory Disease ◽  
Joint Disease ◽  
Bone Pathology ◽  
Novel Target ◽  
Death Receptor 3

Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints that is associated with cartilage and bone destruction. Death Receptor 3 (DR3), a tumor necrosis factor (TNF) receptor superfamily member, has recently been associated with the pathogenesis of RA. We demonstrate that absence of DR3 confers resistance to the development of adverse bone pathology in experimental antigen-induced arthritis (AIA). DR3ko mice exhibited a reduction in all histopathological hallmarks of AIA but, in particular, failed to develop subchondral bone erosions and were completely protected from this characteristic of AIA. In contrast, TNF-like protein 1A (TL1A), the ligand for DR3, exacerbated disease in a dose- and DR3-dependent fashion. Analysis of osteoclast number within AIA joint revealed a reduction in areas susceptible to bone erosion in DR3ko mice, whereas in vitro osteoclastogenesis assays showed that TL1A could directly promote osteoclastogenesis in mouse and man. Treatment with antagonistic anti-TL1A mAb protected animals in a systemic model of RA disease collagen-induced arthritis. We therefore conclude that the DR3–TL1A pathway regulates joint destruction in two murine models of arthritis and represents a potential novel target for therapeutic intervention in inflammatory joint disease.

scholarly journals Brain Endothelial miR-146a Negatively Modulates T-Cell Adhesion through Repressing Multiple Targets to Inhibit NF-κB Activation

2015 ◽  
Vol 35 (3) ◽  
pp. 412-423 ◽  
Author(s):  
Dongsheng Wu ◽  
Camilla Cerutti ◽  
Miguel A Lopez-Ramirez ◽  
Gareth Pryce ◽  
Josh King-Robson ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Nuclear Translocation ◽  
Leukocyte Adhesion ◽  
Cell Types ◽  
Nuclear Factor ◽  
Autoimmune Encephalomyelitis ◽  
Activated T Cells ◽  
Cytokine Activation

Pro-inflammatory cytokine-induced activation of nuclear factor, NF-κB has an important role in leukocyte adhesion to, and subsequent migration across, brain endothelial cells (BECs), which is crucial for the development of neuroinflammatory disorders such as multiple sclerosis (MS). In contrast, microRNA-146a (miR-146a) has emerged as an anti-inflammatory molecule by inhibiting NF-κB activity in various cell types, but its effect in BECs during neuroinflammation remains to be evaluated. Here, we show that miR-146a was upregulated in microvessels of MS-active lesions and the spinal cord of mice with experimental autoimmune encephalomyelitis. In vitro, TNFα and IFNγ treatment of human cerebral microvascular endothelial cells (hCMEC/D3) led to upregulation of miR-146a. Brain endothelial overexpression of miR-146a diminished, whereas knockdown of miR-146a augmented cytokine-stimulated adhesion of T cells to hCMEC/D3 cells, nuclear translocation of NF-κB, and expression of adhesion molecules in hCMEC/D3 cells. Furthermore, brain endothelial miR-146a modulates NF-κB activity upon cytokine activation through targeting two novel signaling transducers, RhoA and nuclear factor of activated T cells 5, as well as molecules previously identified, IL-1 receptor-associated kinase 1, and TNF receptor-associated factor 6. We propose brain endothelial miR-146a as an endogenous NF-κB inhibitor in BECs associated with decreased leukocyte adhesion during neuroinflammation.

scholarly journals Effects of Portabella mushrooms on collagen-induced arthritis, inflammatory cytokines, and body composition in dilute brown non-agouti (DBA1) mice

2011 ◽  
Vol 1 (9) ◽  
pp. 279
Author(s):  
Sandra Peterson ◽  
Edralin A. Lucas ◽  
Djibril Traore ◽  
Lawrance Christopher ◽  
Christine French ◽  
...  
Keyword(s):  
Body Composition ◽  
Mass Loss ◽  
Inflammatory Cytokines ◽  
Fat Mass ◽  
Lean Mass ◽  
Cell Function ◽  
Bone Erosion ◽  
Collagen Induced Arthritis ◽  
Tnf Α

Background: Exotic mushrooms have long been used in Asia for treatment and/or prevention of chronic diseases due to their immunomodulatory properties. However, the health benefits of portabella mushrooms (PM) (brown Agaricus bisporous), on collagen-induced arthritis (CIA) and associated complications, (i.e. loss of lean mass, increased fat mass and inflammatory cytokines), have not been previously investigated.Methods: We investigated CIA pathogenesis, body composition and plasma levels of IL- 6, TNF-α and sICAM1 in DBA1 female mice fed either the AIN76 diet or the same diet fortified with 5% lyophilized PM (n=19-20/group). Ten mice/group were immunized with 100 µg bovine collagen type II on day 42 of the protocol, followed by 50 µg lipopolysaccharides on day 62, and euthanized on day 73-74. Cytokines were measured by ELISA.Results: Compared to baseline diet, PM had: no protective effect from CIA since all collagen-immunized mice developed severe edema, bone erosion, and mononuclear cell infiltration in paws. In mice with and those without CIA, feeding a PM-fortified diet resulted in higher percent of body fat than feeding the baseline diet (p<0.05). After CIA induction, PM provided the following beneficial effects: (a) a smaller reduction in lean mass and absolute thymus weight; (b) a higher fat mass loss; and (c) lower plasma TNF-α levels (p <0.05). PM-fortification did not alter plasma IL-6 and sICAM1 regardless of CIA status; but it increased in vitro IL-6 secretion by mitogen-treated spleen cells.Conclusion: Our data suggest that PM may reduce plasma TNF-α, attenuate lean mass loss and thymus atrophy associated with arthritis, and protect spleen cell function assessed by IL-6 secretion. However, PM-fortification did not attenuate overall CIA pathogenesis which may be due to lack of effect on plasma IL-6. Decreased TNF-α without alterations in IL-6 may reduce the risk of other conditions associated with chronic inflammation such as cardiovascular disease.Key words: portabella mushrooms, inflammatory cytokines, collagen-induced arthritis, body composition, TNF-α, IL-6, thymus, DBA1 mice.

Sign in / Sign up

Export Citation Format

Share Document