Intratracheal injection of LPS and cytokines. V. LPS induces expression of LIF and LIF inhibits acute inflammation

Ulich, Thomas R.; Fann, Ming‐Ji; Patterson, Paul H.; Williams, J. H.; Samal, Babru; Castillo, Juan; Su, Yin; Guo, Kaizhi; Remick, Daniel G.

doi:10.1152/ajplung.1994.267.4.l442

Cited by 50 publications

(52 citation statements)

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“…An enhanced secretion of all these molecules by macrophages was reported upon LPS stimulation (47)(48)(49)(50). Nevertheless, in our hands, addition of TNF-␣ did not affect the replication of X4 primary HIV-1 isolates.…”

Section: Discussioncontrasting

confidence: 50%

Inhibition of CXCR4-Tropic HIV-1 Infection by Lipopolysaccharide: Evidence of Different Mechanisms in Macrophages and T Lymphocytes

Verani¹,

Sironi²,

Siccardi

et al. 2002

The Journal of Immunology

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Bacterial LPS protects primary human macrophages from infection by CCR5-tropic HIV-1 isolates through the release of the CC chemokines RANTES and macrophage inflammatory protein-1α and -1β. Here, we show that LPS also suppresses infection of macrophages by CXCR4-tropic HIV-1 isolates. A marked down-regulation of both CD4 and CXCR4 expression was associated with this effect. Furthermore, a soluble factor(s) released by macrophages upon LPS treatment inhibited infection with CXCR4-tropic HIV-1 isolate viruses in both macrophages and T lymphocytes. Infection of both cell types appeared to be blocked at the level of viral entry and was independent of stromal cell-derived factor-1, the only known natural ligand of CXCR4. Moreover, the suppressive effect of LPS was unrelated to the release of IFN-α and -β, macrophage-derived chemokine, leukemia inhibitory factor, or TNF-α. These results suggest the existence of potent HIV-1 inhibitory factor(s), uncharacterized to date, released by activated cells of the mononuclear phagocytic system.

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Section: Discussioncontrasting

confidence: 50%

Inhibition of CXCR4-Tropic HIV-1 Infection by Lipopolysaccharide: Evidence of Different Mechanisms in Macrophages and T Lymphocytes

Verani¹,

Sironi²,

Siccardi

et al. 2002

The Journal of Immunology

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“…Hyperoxia-induced lung injury, which is exacerbated in the absence of alveolar epithelial STAT3 (10), is ameliorated when LIF is overexpressed in the lungs (53). Similarly, intratracheal administration of recombinant LIF protects rats from hyperoxia-induced lung injury (54) and inhibits LPS-induced pulmonary inflammation (55). The roles of endogenous LIF are less clear.…”

Section: Discussionmentioning

confidence: 99%

Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense during Escherichia coli Pneumonia

Quinton¹,

Jones²,

Robson³

et al. 2008

Am J Respir Cell Mol Biol

102

138

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While signal transducer and activator of transcription (STAT) 3 signaling has been linked to multiple pathways influencing immune function and cell survival, the direct influence of this transcription factor on innate immunity and tissue homeostasis during pneumonia is unknown. Human patients with dominant-negative mutations in the Stat3 gene develop recurrent pneumonias, suggesting a role for STAT3 in pulmonary host defense. We hypothesized that alveolar epithelial STAT3 is activated by IL-6 family cytokines and is required for effective responses during gram-negative bacterial pneumonia. STAT3 phosphorylation was increased in pneumonic mouse lungs and in murine lung epithelial (MLE)-15 cells stimulated with pneumonic bronchoalveolar lavage fluid (BALF) through 48 hours of Escherichia coli pneumonia. Mice lacking active STAT3 in alveolar epithelial cells (Stat3 D/D ) had fewer alveolar neutrophils and more viable bacteria than control mice early after intratracheal E. coli. By 48 hours after E. coli infection, however, lung injury was increased in Stat3 D/D mice. Bacteria were cleared from lungs of both genotypes, albeit more slowly in Stat3 D/D mice. Of the IL-6 family cytokines measured in lungs from infected C57BL/6 mice, IL-6, oncostatin M, leukemia inhibitory factor (LIF), and IL-11 were significantly elevated. Neutralization studies demonstrated that LIF and IL-6 mediated BALF-induced STAT3 activation in MLE-15 cells. Together, these results indicate that during E. coli pneumonia, select IL-6 family members activate alveolar epithelial STAT3, which functions to promote neutrophil recruitment and to limit both infection and lung injury.Keywords: lung; neutrophils; STAT3; pneumonia; cytokines Lung infections account for a tremendous burden of disease worldwide and are a leading cause of acute lung injury (1, 2). While Streptococcus pneumoniae is the most common agent in patients with community-acquired pneumonia (3), gram-negative rods such as Escherichia coli are a frequent cause of nosocomial pneumonia (4). Elimination of these and other pathogens from the lower respiratory tract is made possible by an effective innate immune response (5), which is necessary yet potentially dangerous to the infected host. For this reason, cytokine networks, neutrophil emigration, plasma extravasation, and other characteristics of acute inflammation must be precisely regulated to maintain tissue homeostasis.The STAT3 transcription factor influences both immunity and inflammatory injury, but the importance of STAT3 signaling during pneumonia is unknown. STAT3 activity has been attributed both inflammatory (6-9) and anti-inflammatory (10-12) roles. Likewise, the cytokine interleukin (IL)-6, which largely signals through STAT3 (13, 14), has also been described as both pro-(15-19) and anti-inflammatory (16, 20-22), depending on the biological context. During E. coli pneumonia, neutrophil recruitment and bacterial clearance are impaired in IL-6-deficient mice (15). While the mechanisms through which IL-6 functions during this i...

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“…Surprisingly, LIF injection prior to a challenge with a high dose of LPS protects against the lethal effects of endotoxin [96,97], suggesting that LIF may also exert anti-inflammatory activities. Similarly, intratracheal coinjection of LIF and LPS inhibits the acute inflammatory response that is usually triggered by LPS alone [98]. Infiltration of neutrophils into the lung is affected, and LIF significantly reduces the amount of TNF secreted into the bronchoalveolar fluid.…”

Section: Lif In Acute and Chronic Inflammationmentioning

confidence: 99%

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

1999

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Inflammation refers to a complex set of mechanisms by which tissues respond to injury and infection. Among the many soluble mediators associated with this process, cytokines are known to be crucial in regulating a variety of cellular and molecular events. Leukemia inhibitory factor (LIF), interleukin 6 (IL-6), IL-11, and possibly other members of this cytokine family are key mediators in various inflammatory processes such as the acute-phase reaction, tissue damage, and infection. These cytokines can act in both pro-inflammatory and anti-inflammatory ways, depending on a number of variables. We emphasize here recent work utilizing knockout mice, which has highlighted the roles of LIF and IL-6, particularly in interactions between the immune and nervous systems.

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Intratracheal injection of LPS and cytokines. V. LPS induces expression of LIF and LIF inhibits acute inflammation

Cited by 50 publications

References 0 publications

Inhibition of CXCR4-Tropic HIV-1 Infection by Lipopolysaccharide: Evidence of Different Mechanisms in Macrophages and T Lymphocytes

Inhibition of CXCR4-Tropic HIV-1 Infection by Lipopolysaccharide: Evidence of Different Mechanisms in Macrophages and T Lymphocytes

Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense during Escherichia coli Pneumonia

Leukemia Inhibitory Factor, Interleukin 6, and Other Cytokines Using the GP130 Transducing Receptor: Roles in Inflammation and Injury

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