Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to determine the effects of interleukin-1 (IL-1) on human thyroid epithelial cells (thyrocytes) and whether thyrocytes produce IL-1. The supernatants of cultured peripheral blood monocytes stimulated with lipopolysaccharide (LPS) increased [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Grave's disease. The IL-1 levels of cultured supernatants of monocytes were measured by a thymocyte costimulation assay and a solid phase sandwich immunoenzymometric assay. The supernatants of monocyte cultures stimulated with LPS contained significant amounts of IL-1 bioactivity and IL-1 alpha and IL-1 beta immunoactivity. Recombinant IL-1 beta (rIL-1 beta) also stimulated [3H]thymidine incorporation into thyrocytes from normal subjects and patients with Graves' disease, and it increased the proportion of thyrocytes in the S phase of the cell cycle. Furthermore, thyrocytes stimulated with rIL-1 beta for 24 h produced significant amounts of prostaglandin E2. Indomethacin inhibited completely the rIL-1 beta-stimulated prostaglandin E2 production and increased markedly [3H]thymidine incorporation. IL-1-like activity also was detected in the cultured supernatants of lipopolysaccharide (LPS)-stimulated thyrocytes from Graves' and normal thyroid glands, but the amount of IL-1-like activity secreted by thyrocytes was significantly less than that secreted by circulating monocytes. The kinetics of the release of IL-1-like activity by thyrocytes were similar to those of its production by circulating monocytes. Pretreatment of thyrocytes with interferon-gamma failed to enhance the release of IL-1-like activity. Moreover, IL-1 alpha or IL-1 beta immunoreactivity could not be detected in the supernatants of LPS-stimulated thyrocytes, despite the presence of IL-1-like bioactivity. No IL-1 alpha mRNA was detected in unstimulated thyrocytes or thyrocytes stimulated with LPS and phorbol myristate acid. These findings demonstrate that thyrocytes produce an IL-1-like substance(s), but not IL-1, when stimulated by LPS. We conclude that IL-1 may regulate the proliferation of thyrocytes and that local production of IL-1 by infiltrating monocytes may contribute to the development of goiter in patients with autoimmune thyroid diseases.
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PMID:Interleukin-1 production and action in thyroid tissue. 265 35

Cytokine production was studied in thyroid tissue from patients with Graves' disease, Hashimoto's thyroiditis and non-toxic goitre. The expression of interferon gamma, tumour necrosis factor alpha and beta, interleukin-1 alpha and beta, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1 alpha and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1 alpha and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vivo as both interleukin-1 and interleukin-6 facilitate T cell activation.
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PMID:Analysis of intrathyroidal cytokine production in thyroid autoimmune disease: thyroid follicular cells produce interleukin-1 alpha and interleukin-6. 268 Jan 82

In the course of studies of cell-mediated immunity in Graves' disease, we noted that normal peripheral blood monocytes, when stimulated by bacterial lipopolysaccharide, conditioned their media with a factor that had the physicochemical properties of the lymphokine interleukin-1 (IL-1) and that enhanced DNA synthesis and replication in quiescent FRTL5 cells, a line of nontransformed rat thyroid follicular cells. This finding led to the present studies, in which the effect of IL-1 (recombinant IL-1-p) on DNA synthesis in FRTL5 was explored. In the absence of serum, IL-1 induced a small, but significant, increase in [3H]thymidine incorporation into DNA. Calf serum (0.5%) alone also stimulated DNA synthesis slightly, but it greatly enhanced, in a synergistic manner, the stimulatory response to IL-1, decreasing the minimally effective concentration of IL-1 and amplifying the response to higher concentrations. A similar synergism was noted when quiescent FRTL5 were cultured with a combination of IL-1 and a low concentration of insulin-like growth factor-I (IGF-I), which itself stimulated DNA synthesis modestly. IL-1 also increased levels of the mRNA of the proto-oncogene c-myc in quiescent FRTL5, as TSH does, an effect thought to reflect commitment of the cell to increased growth. The findings indicate that IL-1 is an independent stimulator of thyroid cell growth, and that its effects are greatly enhanced by serum, probably in large measure by the IGF-I contained therein. They raise the possibility that IL-1 generated locally by intrathyroid macrophages may act directly by a short-loop mechanism to increase goiter formation in autoimmune thyroid disease.
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PMID:Interleukin-1 stimulates thyroid cell growth and increases the concentration of the c-myc proto-oncogene mRNA in thyroid follicular cells in culture. 349 69