Search

Granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced human monocyte-derived macrophage (GM-Mφ) or macrophage CSF (M-CSF)-induced human monocyte-derived Mφ (M-Mφ) are distinct in terms of the resistance to Mycobacterium tuberculosis. To elucidate the role of molecules involved in the functional differences between these Mφs, we investigated the gene expression profiles using microarray. After culture of CD14+ monocytes with CSFs, Mφs were cultured with or without bacillus Calmette–Guérin (BCG) (GM-Mφ-BCG and M-Mφ-BCG). The gene expression profiles from these cells were compared. Chemokines highly expressed in M-Mφs were selected and evaluated for anti-mycobacterial activity and superoxide production. FN1 and FCGR2B were the most up-regulated genes in GM-Mφ and M-Mφ, respectively. After stimulation with BCG, three chemokine genes ( Osteopontin ( SPP1), CXC chemokine ligand 7 ( CXCL7) and CC chemokine ligand 11 ( CCL11)) were highly expressed in M-Mφ-BCG when compared to those in GM-Mφ-BCG. A significantly increased resistance to M. tuberculosis H37Ra was observed after the stimulation of GM-Mφ with SPP1 or CXCL7. Superoxide production levels of SPP1- or CXCL7-stimulated GM-Mφs were higher than those of GM-Mφs without stimulation. These results indicate that both SPP1 and CXCL7 might have a role in the resistance against mycobacteria, at least in part, through augmenting reactive oxygen intermediate production in Mφs. [ABSTRACT FROM AUTHOR]

An autosomal recessive gene, lpr, is responsible for lymphoproliferation and autoimmunity of lpr mice, in which background genes are also known to influence the development of autoimmune disease. To define the differences in abnormally proliferating T cells between C57BL/6-lpr/lpr and MRL/Mp-lpr/lpr mice, and to try and understand the influence of background in the differing expression of autoimmune disease in both strains, we analysed the sequences of T cell antigen receptor Vβ genes expressed in the cells from the enlarged lymph nodes of C57BL/6-lpr/lpr mice. Eleven β cDNAs out of the 38 Cβ-specific cDNAs contained sequences with open reading frames from the beginning of the variable region to the expected termination codons at the end of the constant regions. Notably, 36% of the functional β-chain mRNAs expressed Vβ8.3 genes, whereas Vβ8.3 and Vβ8.2 genes were not found. These results are consistent with a relatively lower frequency of the Vβ8.1 or Vβ8.2 expressing cells in the hypertrophic lymph nodes of C57BL/6-lpr/lpr mice, detected by KJI6-133 monoclonal antibody. Interestingly, other Vβ genes expressed in these mice were completely distinct from those in MRL/Mp-lpr/lpr mice as described by Singer et al (1986), The different distribution of Vβ genes expressed in C57BL/6-lpr/lpr from that in MRL/Mp-lpr/lpr mice might be related to the differences in the genetic background and the expression of lpr gene-associated autoimmunity. [ABSTRACT FROM AUTHOR]

We previously reported that the number of TNF-α-producing cells was increased in the liver of patients with type C chronic liver disease. To understand further the pathophysiology of this change, we examined serum levels of two soluble TNF receptors, TNF-αRI (p55)and -αRII (p75), and IL-10, all of which act as TNF-α buffer, and IL-15, a novel cytokine sharing many immunological activities with IL- 2, using ELISA methods. We studied control individuals and patients with type C chronic liver disease, including asymptomatic hepatitis C virus (HCV) carriers with persistently normal serum ALT values, and those with chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Both types of sTNF-αR closely correlated with disease progression. Patients with LC and HCC had significantly elevated levels for sTNF-αRII compared with the other patient groups and controls. Serum IL-10 levels were significantly greater in all chronic liver disease groups than in controls. With respect to IL-15, the values were high in CH, LC and HCC compared with those of controls. Notably, HCC patients showed highest values for both IL-10 and IL-15, with significant differences from the other patient groups. Serial determinations revealed that interferon (IFN) treatment for CH patients resulted in the suppression of circulating lL-10 and IL-15 levels along with decrease in serum aminotransferase values. Both cytokines remained at decreased levels after cessation of therapy in patients who went into clinical and virological remission. On the other hand, treatment did not affect serum levels of sTNF-αRs, These findings indicate that serum levels of these molecules correlated with disease progress in chronic HCV infection, and that IL-10 and IL-15 may reflect the degree of inflammation in the liver. It is also suggested that both cytokines may be related to the development of HCC. [ABSTRACT FROM AUTHOR]