Interleukin-10 Modulates Proinflammatory Cytokines in the Human Monocytic Cell Line THP-1 Stimulated with<i>Borrelia burgdorferi</i>Lipoproteins

Murthy, P. K.; Dennis, Vida A.; Lasater, Barbara L.; Philipp, Mario T.

doi:10.1128/iai.68.12.6663-6669.2000

Cited by 85 publications

(70 citation statements)

References 69 publications

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“…Exogenous TNF-␣ has been reported to augment IL-10 production in monocytes [40], and IL-10 has also been demonstrated to suppress LPS-induced IL-6 and IL-12 production [41]. We considered the possibility that enhanced production of TNF-␣ by p110␣-deficient cells might have led to augmented IL-10 production through a paracrine effect and that this may have led to suppression of IL-6 and IL-12.…”

Section: Discussionmentioning

confidence: 99%

“…5D) production by p110␣-deficient cells to control levels. IL-10 has also been reported to suppress LPS-induced IL-6 and IL-12 production [41]. To investigate whether diminished LPS-induced IL-6 and IL-12 secretion by p110␣-deficient THP-1 cells was a result of enhanced IL-10 production, neutralizing antibody to IL-10 was added or not prior to stimulation of cell with LPS (Fig.…”

Section: Lps-induced Cytokine Production In Thp-1 Cells Is Mediated Tmentioning

confidence: 99%

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Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production

Lee

Nauseef

Moeenrezakhanlou

et al. 2007

Journal of Leukocyte Biology

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Mononuclear phagocytes are critical modulators and effectors of innate and adaptive immune responses, and PI-3Ks have been shown to be multifunctional monocyte regulators. The PI-3K family includes eight catalytic isoforms, and only limited information is available about how these contribute to fine specificity in monocyte cell regulation. We examined the regulation of phagocytosis, the phagocyte oxidative burst, and LPSinduced cytokine production by human monocytic cells deficient in p110␣ PI-3K. We observed that p110␣ PI-3K was required for phagocytosis of IgG-opsonized and nonopsonized zymosan in differentiated THP-1 cells, and the latter was inhibitable by mannose. In contrast, p110␣ PI-3K was not required for ingestion serum-opsonized zymosan. Taken together, these results suggest that Fc␥R-and mannose receptor-mediated phagocytosis are p110␣-dependent, whereas CR3-mediated phagocytosis involves a distinct isoform. It is notable that the phagocyte oxidative burst induced in response to PMA or opsonized zymosan was also found to be dependent on p110␣ in THP-1 cells. Furthermore, p110␣ was observed to exert selective and bidirectional effects on the secretion of pivotal cytokines. Incubation of p110␣-deficient THP-1 cells with LPS showed that p110␣ was required for IL-12p40 and IL-6 production, whereas it negatively regulated the production of TNF-␣ and IL-10. Cells deficient in p110␣ also exhibited enhanced p38 MAPK, JNK, and NF-B phosphorylation. Thus, p110␣ PI-3K appears to uniquely regulate important monocyte functions, where other PI-3K isoforms are uninvolved or unable to fully compensate. J. Leukoc. Biol. 81: 1548 -1561; 2007.

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Section: Discussionmentioning

confidence: 99%

Section: Lps-induced Cytokine Production In Thp-1 Cells Is Mediated Tmentioning

confidence: 99%

Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production

Lee

Nauseef

Moeenrezakhanlou

et al. 2007

Journal of Leukocyte Biology

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“…There is evidence pointing to the importance of a T H 1/T H 2 balance, because increased IL-12 and T H 1-type cytokines are associated with disease progression in humans and susceptible strains of inbred mice (12)(13)(14)(15), whereas cytokines such as IL-10 have a beneficial effect (16)(17)(18)(19). In contrast, Bockenstedt et al (20) have shown that CD4 ϩ T H 1 cells were beneficial for the regression of carditis.…”

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confidence: 99%

NKT cells prevent chronic joint inflammation after infection withBorrelia burgdorferi

Tupin

Benhnia

Kinjo

et al. 2008

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

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Borrelia burgdorferi is the etiologic agent of Lyme disease, a multisystem inflammatory disorder that principally targets the skin, joints, heart, and nervous system. The role of T lymphocytes in the development of chronic inflammation resulting from B. burgdorferi infection has been controversial. We previously showed that natural killer T (NKT) cells with an invariant (i) TCR ␣ chain (iNKT cells) recognize glycolipids from B. burgdorferi, but did not establish an in vivo role for iNKT cells in Lyme disease pathogenesis. Here, we evaluate the importance of iNKT cells for host defense against these pathogenic spirochetes by using V␣14i NKT cell-deficient (J␣18 ؊/؊ ) BALB/c mice. On tick inoculation with B. burgdorferi, J␣18 ؊/؊ mice exhibited more severe and prolonged arthritis as well as a reduced ability to clear spirochetes from infected tissues. V␣14i NKT cell deficiency also resulted in increased production of antibodies directed against both B. burgdorferi protein antigens and borrelial diacylglycerols; the latter finding demonstrates that anti-glycolipid antibody production does not require cognate help from V␣14i NKT cells. V␣14i NKT cells in infected wild-type mice expressed surface activation markers and produced IFN␥ in vivo after infection, suggesting a participatory role for this unique population in cellular immunity. Our data are consistent with the hypothesis that the antigen-specific activation of V␣14i NKT cells is important for the prevention of persistent joint inflammation and spirochete clearance, and they counter the long-standing notion that humoral rather than cellular immunity is sufficient to facilitate Lyme disease resolution.cytokines ͉ glycolipids ͉ Lyme disease ͉ spirochetes

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“…IL-10 is known to suppress a number of different immune cell types, and its main biological role appears to involve reducing and eventually terminating inflammatory responses (61). M responses are potently suppressed by IL-10, and because M are believed to play a central role in both the innate and adaptive immune responses to B. burgdorferi, it is possible that M are better able to eradicate spirochetes in the absence of the substantial IL-10 amounts elicited in response to B. burgdorferi by B6 mice (60,62,63). Alternatively, our previous studies also showed that infected IL-10 Ϫ/Ϫ mice possessed significantly higher levels of B. burgdorferi-specific, as well as total, Ab levels compared with infected B6 mice (60), so it is possible that much of the increased clearance is mediated by this enhanced Ab response.…”

mentioning

confidence: 99%

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

Lazarus

Meadows

Lintner

et al. 2006

The Journal of Immunology

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Borrelia burgdorferi is capable of persistently infecting a variety of hosts despite eliciting potent innate and adaptive immune responses. Preliminary studies indicated that IL-10-deficient (IL-10−/−) mice exhibit up to 10-fold greater clearance of B. burgdorferi from target tissues compared with wild-type mice, establishing IL-10 as the only cytokine currently known to have such a significant effect on spirochetal clearance. To further delineate these IL-10-mediated immune effects, kinetic studies indicated that spirochete dissemination to target tissues is similar in both wild-type and IL-10−/− mouse strains, and that enhanced clearance of B. burgdorferi in IL-10−/− mice is correlated with increased B. burgdorferi-specific Ab as early as 2 wk postinfection. Immunoblot analysis indicated that Abs produced by infected IL-10−/− and wild-type mice recognize similar ranges of spirochetal Ags. Immune sera from IL-10−/− and wild-type mice also exhibited similar bactericidal activity in vitro, and passive transfer of these immune sera into B. burgdorferi-infected SCID mice caused similar reductions of bacterial numbers in target tissues. Infectious dose studies indicated that 8-fold more B. burgdorferi were needed to efficiently infect naive IL-10−/− mice, suggesting these animals possess higher innate barriers to infection. Moreover, macrophages derived from IL-10−/− mice exhibit enhanced proinflammatory responses to B. burgdorferi stimulation compared with wild-type controls, and these responses are not significantly affected by the presence of immune serum. These findings confirm that B. burgdorferi clearance by innate immune responses is more efficient in the absence of IL-10, and these activities are not directly related to increased levels of B. burgdorferi-specific Ab.

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Interleukin-10 Modulates Proinflammatory Cytokines in the Human Monocytic Cell Line THP-1 Stimulated withBorrelia burgdorferiLipoproteins

Abstract: We determined previously that lipoproteins of

Cited by 85 publications

References 69 publications

Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production

Monocyte p110α phosphatidylinositol 3-kinase regulates phagocytosis, the phagocyte oxidase, and cytokine production

NKT cells prevent chronic joint inflammation after infection withBorrelia burgdorferi

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

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