Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE(2), a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE(2) via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE(2) production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-kappaB. Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-kappaB in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-kappaB pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.
Genetic factors seem to play a significant role in susceptibility to systemic lupus erythematosus (SLE). We previously described the amino acid polymorphism (Val14Met) within the IFN-gamma receptor 1 (IFN-gammaRI), and that the frequency of the Metl4 allele in SLE patients was significantly higher than that of the healthy control population [Tanaka et al. (1999) Immunogenetics 49, 266-271]. We also found an amino acid polymorphism (Gln64Arg) within IFN-gamma receptor 2 (IFN-gammaR2). Since the IFN-gamma receptor is a complex consisting of IFN-gammaR1 and IFN-gammaR2, we searched for the particular combination of two kinds of amino acid polymorphisms found within the IFN-gamma receptor which plays a prominent role in susceptibility to SLE. The greatest risk of the development of SLE was detected in the individuals who had the combination of IFNGR1 Met14/Val14 genotype and IFNGR2 Gln64/Gln64 genotype.
To assess the association between polymorphisms within the interleukin-10 receptor cDNA gene (IL10R) and systemic erythematosus (SLE) in Japanese people.We examined the IL-10 receptor genotype of 109 SLE patients and 102 healthy subjects by the reverse transcription-polymerase chain reaction-restriction fragment length polymorphism (RT-PCR-RFLP) method.There was no difference in the IL10R genotype frequencies of these two groups.The IL10R genotype does not determine susceptibility to SLE in Japanese people.
Dust particles were collected from the dust box of a wet- or dry-type dust-collecting apparatus attached to a heating furnace for the burning of animal bodies and excreta. They were analyzed for constituent elements both qualitatively and quantitatively. Analysis was carried out by two instruments, a flat diffraction-spectrum camera and an atomic extinction spectrophotometer. As a result, it was clarified that Ca, Fe, Mg, and Si showed high concentrations as main constituent elements of dust particles. There was a tendency for the concentration of elements contained to be higher in dust particles collected from the dry-type dust-collecting apparatus than in those from the wet-type one. It was demonstrated that the Fe content was high in dust particles collected from the wet-type dust-collecting apparatus. Such elements as Al, B, Cd, Cr, Mg, Mn, P, Pb, Si, V, and Zn have been regarded as particularly injurious substances for respiration in living enviroment. They were proved to have been contained in dust particles collected from the burning furnace where animal bodies and excreta had been burned.
