Cultures of astrocytes and microglia express interleukin 18

Conti, Bruno; Park, Larry C.H.; Calingasan, Noel Y.; Kim, Yoonseong; Kim, Ho-Cheol; Bae, Young-Soo; Gibson, Gary E.; Joh, Tong H.

doi:10.1016/s0169-328x(99)00034-0

Cited by 168 publications

(108 citation statements)

References 31 publications

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“…Thus, we assessed IL-18 in the K/ BxN model and found increased spinal IL-18 mRNA levels subsequent to induction of arthritis, which is in line with mutual production mechanisms with IL-1β. From our data it is not evident which cell types are responsible for the increased spinal cytokine production, but earlier data indicate that cells of glial origin have the capacity to produce both IL-1β and IL-18 (29,42) and have proven to be activated in response to experimental arthritis (8). The difference in spinal TNF mRNA levels in experimental arthritis compared with unchanged TNF levels in RA CSF may be explained by the known discrepancies concerning production of cell-bound, versus soluble, TNF in the CNS (43).…”

Section: Discussioncontrasting

confidence: 81%

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Lampa

Westman

Kadetoff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

138

103

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During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.

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Section: Discussioncontrasting

confidence: 81%

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Lampa

Westman

Kadetoff

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

138

103

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“…It has been shown that IL-18, a downstream mol-ecule of P2X 7 R, is mainly produced by microglia [47,48] . The present results showed that the microglial inhibitor minocycline not only inhibited TSS-induced spinal LTP but also reduced the increase in microglial IL-18 expression induced by TSS.…”

Section: Discussionmentioning

confidence: 99%

Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation

Chu

Zhang

2012

Neurosci. Bull.

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Immunohistochemistry showed that minocycline inhibited the sequential activation of microglia and astrocytes, and IL-18 was predominantly colocalized with the microglial marker Iba-1 in the spinal superficial dorsal horn. Western blot revealed that repeated intrathecal injection of minocycline significantly inhibited the increased expression of IL-18 and IL18Rs in microglia induced by TSS. Conclusion The IL-18 signaling pathway in microglia is involved in TSS-induced spinal LTP and mechanical allodynia.

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“…Gene expression and/or protein secretion of IL-18 have been observed in macrophages (9), dendritic cells (10), mononuclear cells (11), keratinocytes (12), osteoblast cells (13), pituitary gland and adrenal cortical cells (14), astrocytes and microglia (15), and intestinal epithelial cells (7,8). It is also known that both precursor and mature forms of IL-18 exist.…”

mentioning

confidence: 99%

Chlamydia trachomatis Infection of Epithelial Cells Induces the Activation of Caspase-1 and Release of Mature IL-18

Shen

Brunham

2000

The Journal of Immunology

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Th1 cells that secrete IFN-γ are particularly important in protective immunity against intracellular pathogens, including chlamydiae, and IL-18 together with IL-12 are strong inducers of IFN-γ secretion by CD4 T cells. Because epithelial cells are known to synthesize IL-18, we investigated the effects of Chlamydia trachomatis infection of human epithelial cell lines on IL-18 secretion. We confirmed that several human epithelial cell lines constitutively express pro-IL-18 and that C. trachomatis infection causes cells to secrete mature IL-18. This was observed for several different serovars and biovars of C. trachomatis. Chlamydia-induced secretion of IL-18 from epithelial cells was regulated at the posttranscriptional level and was dependent on the activation of caspase-1. IL-1α or other secreted factor(s) from chlamydia-infected epithelial cells as well as chlamydial structural component(s) were not involved in inducing IL-18 secretion. Activation of caspase-1 and increased secretion of mature IL-18 was correlated with chlamydial, but not with host protein synthesis. In contrast to epithelial cell lines, fibroblast cell lines constitutively expressed much lower levels of pro-IL-18 and did not secrete mature IL-18 after chlamydial infection even though caspase-1 was activated. Taken together, the results suggest that a chlamydia-derived factor(s) is essential for the secretion of mature IL-18 through caspase-1 activation in infected epithelial cells.

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Cultures of astrocytes and microglia express interleukin 18

Cited by 168 publications

References 31 publications

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice

Involvement of microglia and interleukin-18 in the induction of long-term potentiation of spinal nociceptive responses induced by tetanic sciatic stimulation

Chlamydia trachomatis Infection of Epithelial Cells Induces the Activation of Caspase-1 and Release of Mature IL-18

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