The effect of inflammatory cytokines on secretion of macrophage colony-stimulating factor and monocyte chemoattractant protein-1 in human granulosa cells

PROBLEM: In order to investigate the role of macrophage colony-stimulating factor (M-CSF) and monocyte chemoattractant protein -1 (MCP-1) in human ovulation, we studied the regulation of M-CSF and MCP-1 in cultured human granulosa cells. METHOD OF STUDY: Immortalized granulosa cells (GC1a) were cultured in serum-free medium, and incubated with interleukin (IL)-1alpha, IL-1 receptor antagonist (ra) and tumor necrosis factor (TNF)-alpha. The supernatants were collected, and M-CSF and MCP-1 were measured by ELISA. RESULTS: The levels of M-CSF and MCP-1 were increased after treatment with IL-1alpha (1 nm) and TNF-alpha (1 nm) in a time-dependent manner. The levels of M-CSF and MCP-1 were significantly increased after treatment with IL-1alpha and TNF-alpha in a dose-dependent manner. However, the levels of M-CSF and MCP-1 were significantly decreased by treatment with IL-1alpha (1 nm) and/or increasing concentrations of IL-1 ra. CONCLUSIONS: Our data indicated that M-CSF and MCP-1 were regulated by IL-1alpha and TNF-alpha. It was suggested that M-CSF and MCP-1 may play an important role in human preovulatory processes.     

Metal ions induce bone-resorbing cytokine production through the redox pathway in synoviocytes and bone marrow macrophages

To evaluate the biological reactions to metal ions potentially released from prosthetic implants, we examined the ability of metal ions to produce bone-resorbing cytokines and the underlying mechanism using synoviocytes and bone marrow (BM) macrophages. The cells were incubated with NiCl(2), CoCl(2), CrCl(3) or Fe(2)(SO(4))(3) at optimal concentrations, which are detectable in joint fluid following total joint arthroplasty. The production of interleukin-1beta, interleukin-6 and tumor necrosis factor-alpha were enhanced by all metal ions tested as determined by enzyme-linked immunosorbent assay. From the results of electrophoresis mobility shift assay, all metal ions enhanced the DNA-binding activity of nuclear factor kappaB (NF-kappaB), and p50-p65 heterodimers and p50 homodimers were the major subunits. These effects of the metal ions were considerably blocked by pyrrolidine dithiocarbamate (PDTC) known as a radical scavenger. An electron spin resonance study clearly demonstrated the ability of metal ions to generate activated oxygen species (AOS), especially hydroxyl radicals (*OH), which accounts for PDTC-blockade of metal ion-induced NF-kappaB activation and subsequent cytokine production. Taken together, our data raised the possibility that small amounts of metal ions released from prosthetic implants activate synoviocytes and BM macrophages through the AOS-mediated process (i.e. the redox pathway), and contribute to the initiation of osteolysis at the bone-implant interface.     

Active matrix metalloproteinases in the tear fluid of individuals with vernal keratoconjunctivitis

Corneal epithelial lesions distinguish vernal keratoconjunctivitis (VKC) from other ocular allergic diseases. Such lesions result from degradation of the corneal epithelial basement membrane, which comprises mostly type IV collagen and laminin. Matrix metalloproteinase 2 (MMP-2) and MMP-9 catalyze the degradation of these 2 extracellular matrix proteins. The possible role of MMP-2 and MMP-9 in the pathogenesis of corneal lesions associated with VKC was investigated by assaying tear fluid for the presence of these enzymes. Tear fluid was collected from 6 eyes of 6 patients with active VKC, 14 eyes of 14 patients with active allergic conjunctivitis, and 6 eyes of 6 nonallergic healthy volunteers. Gelatin zymography revealed that the tear fluid of healthy volunteers contained inactive proforms of both MMP-2 and MMP-9 but not the active forms of these enzymes. Active forms of MMP-2 or MMP-9 were detected in a minority of patients with allergic conjunctivitis. However, with the exception of one individual for whom active MMP-9 was not detected, tear fluid from all patients with VKC contained both proforms and active forms of MMP-2 and MMP-9. These results implicate MMP-2 and MMP-9 in the pathogenesis of corneal epithelial disorders associated with VKC.     

Carbohydrate metabolism in intact golden hamsters infected with plerocercoids of Spirometra erinacei (Cestoda: Diphyllobothriidae)

This study was performed to investigate the mechanism involved in a decrease in the serum glucose of golden hamsters infected with plerocercoids of Spirometra erinacei. The concentration of glucagon, the activity of glucose-6-phosphatase in the liver, and the in vivo incorporation of 2-deoxyd-[1,2-³H]glucose into various organs increased in plerocercoid-infected hamsters compared with controls. Furthermore, the serum from the plerocercoid-infected hamsters enhanced the in vitro incorporation of [U-¹⁴C]glucose into adipose tissues, compared with control serum. The serum levels of immunoreactive insulin and somatomedin associated with nonsuppressible insulin-like activity in experimental animals, however, were not significantly different from those in controls. Therefore, we conclude that the decrease in serum glucose associated with plerocercoid infection is not the result of a decrease in gluconeogenesis, but the result of an increased utilization of glucose in the peripheral tissues.     

Blepharophimosis sequence and de novo balanced autosomal translocation [46, XY,t(3;4)(q23;p15.2)]: Possible assignment of the trait to 3q23

We report on a boy with the blepharophimosis sequence and de novo, apparently balanced reciprocal translocation between 3q23 and 4p15.2 [46, XY,t(3;4)(q23;p15.2)de novo]. Possible assignment of this autosomal dominant disorder is discussed. A 3q23 band is a more preferable gene locus of the blepharophi mosis sequence, based on the comparison of clinical manifestations between 4p- and 3q-syndromes.     

ULTRASTRUCTURE OF AN ANAPLASTIC GIANT-CELL CARCINOMA FOUND 8 YEARS AFTER OPERATION ON A PAPILLARY CARCINOMA OF THE THYROID

Light and electron microscopic studies have been made on an anaplastic giant-cell tumor that developed in a woman 8 years after an operation on the thyroid for papillary carcinoma. Many giant cells were observed in the anaplastic tumor tissue, but no follicles. Numerous tightly-packed mitochondria and abundant ribosomes were present, but there were no desmosomes. The basement membrane was not distinct.     

Expression of interferon-gamma-inducible protein-10 in human endometrial stromal cells

Human endometrial stromal cells (ESC) can produce a variety of chemokines, especially after inflammatory stimulation. Interferon-gamma-inducible protein-10 (IP-10) is a potent chemoattractant for lymphocytes, and belongs to the family of non-ELR CXC chemokines. The expression of IP-10 in ESC after stimulation with interferon-gamma (IFN-gamma), interleukin-1 beta (IL-1 beta), tumour necrosis factor-alpha (TNF-alpha), or lipopolysaccharide (LPS) was evaluated using an enzyme-linked immunosorbent assay and Northern blot analysis. A small amount of IP-10 protein was detected in the culture media of unstimulated ESC. The expression of IP-10 mRNA was detected in ESC. IFN-gamma, IL-1 beta, TNF-alpha and LPS significantly stimulated the expression of IP-10 mRNA and protein in ESC. These results suggest that the production of IP-10 by ESC is regulated by inflammatory mediators. The modulation of IP-10 concentrations in the local environment may contribute to the normal and pathological processes of human reproduction by regulating leukocyte trafficking in the endometrium.     

Ras homolog gene family H (RhoH) deficiency induces psoriasis-like chronic dermatitis by promoting TH17 cell polarization

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Inhibitory effect of antiserum to surface antigen P50 of Babesia gibsoni on growth of parasites in severe combined immunodeficiency mice given canine red blood cells

The inhibitory effect of an antiserum to surface protein P50 of Babesia gibsoni on the growth of the parasite was determined with severe combined immunodeficiency mice given canine red blood cells. The antiserum to the recombinant P50 protein significantly inhibited the parasite growth, indicating that P50 might be a useful vaccine candidate.