Pioglitazone, PPARγ agonist, attenuates experimental autoimmune neuritis.

Recent advances demonstrate peroxisome proliferator-activated receptors gamma (PPARγ) agonist, pioglitazone, as an anti-inflammatory drug. We investigated the effect of pioglitazone on experimental autoimmune neuritis (EAN) rats. Pioglitazone was given once daily (10 mg/kg) by oral gavage feeding from day 1-24 (suppressive group) and day 11-24 (therapeutic group). Pioglitazone ameliorated the clinical score of EAN, decreased expression of TNF-α, IFN-γ, and the activation of NF-κB, while increasing the expression of PPARγ and IL-4. Furthermore, we observed higher expression of PPARγ and IL-4 and lower expression of TNF-α, IFN-γ and reduced activation of NF-κB in suppressive group than those in the therapeutic group, which corresponds to lower clinical score and earlier disease recovery. Our data effectively demonstrate the anti-inflammatory properties of pioglitazone in EAN by inhibition of NF-κB signaling pathway.

Inactivation of TLR9 by a suppressive oligodeoxynucleotides can ameliorate the clinical signs of EAN.

Susceptible-strain animals immunized with P2 peptide could generate the disease of experimental autoimmune neuritis (EAN) with inflammation and demyelination of peripheral nerve. A myriad of transcription factors and inflammatory cytokines have been found to participate in this process; however, the roles of toll-like receptors (TLRs) are poorly understood in EAN. The aim of this study is to explore the role of TLR9 in the pathogenesis of EAN. The EAN was induced in Lewis rat by immunization with P2(53-78) and complete Freund's adjuvant. CpG oligodeoxynucleotides (ODN) (cODN), a suppressive ODN (sODN) and a control non-specific ODN (nODN) were respectively administered to explore the role of TLR9 in EAN both in vivo and vitro. Following immunization up to the peak phase of EAN, EAN rats inoculated with sODN had remarkably better clinical score of EAN and expressed a significantly inhibited TLR9 signaling pathway. Our study suggests that TLR9 may be involved in the pathogenesis of EAN.

Expression of Toll-like receptors 2, 4 and 9 in patients with Guillain-Barré syndrome.

OBJECTIVE: A myriad of transcription factors and inflammatory cytokines have been described to participate in the pathogenesis of Guillain-Barré syndrome (GBS). However, the innate immunity components--Toll-like receptors (TLRs)--have never been explored in this disease. We therefore investigated the expression of TLR2, 4 and 9 in the peripheral circulation of GBS patients as well as healthy controls. METHODS: Twenty-one GBS patients and 21 healthy donors participated in this study. Peripheral blood mononuclear cells were used for mRNA and protein analysis of TLR-related molecules. Also, peripheral blood mononuclear cells from different subjects were incubated with different TLR agonists and the subsequent IFN-γ secretion was determined. RESULTS: Expression of TLR2, 4 and 9 as well as their related signaling molecules were higher in GBS patients compared to healthy controls. Disability scores of GBS patients had a strong positive correlation with the high levels of expression of TLR2, 4 and 9. CONCLUSIONS: The TLR signaling pathway may be involved in the pathogenesis of GBS.