Activation of NF-κB by nontypeable
            <i>Hemophilus influenzae</i>
            is mediated by toll-like receptor 2-TAK1-dependent NIK–IKKα/β–IκBα and MKK3/6–p38 MAP kinase signaling pathways in epithelial cells

Shuto, Tsuyoshi; Xu, Haidong; Wang, Beinan; Han, Jiahuai; Kai, Hirofumi; Gu, Xin; Murphy, Timothy F.; Lim, David J.; Li, Jian Dong

doi:10.1073/pnas.151236098

Cited by 247 publications

(315 citation statements)

References 40 publications

(50 reference statements)

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“…Knock down of MKKs 3 or 6 blocked SF-induced NF-kB activity, suggesting roles for endogenous MKK3/6 in SF-mediated NF-kB signaling, although we did not tested whether these kinases contribute to cell survival. The stress-activated kinase p38 is a substrate for MKK3 and MKK6; and several studies suggest that p38 can stimulate NF-kB signaling (Nick et al, 1999;Shuto et al, 2001;Costantini et al, 2005). Here, we found that a selective inhibitor of p38 (SB202190) inhibited SF-, MKK3/6-and (SF þ V12Ras)-stimulated NF-kB activity, suggesting that an MKK3/6-p38 pathway contributes to SF-stimulated NF-kB activity.…”

Section: Discussionmentioning

confidence: 51%

Ras effector pathways modulate scatter factor-stimulated NF-κB signaling and protection against DNA damage

et al. 2007

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Section: Discussionmentioning

confidence: 51%

Ras effector pathways modulate scatter factor-stimulated NF-κB signaling and protection against DNA damage

et al. 2007

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“…The expression plasmids TLR2 dominant negative (DN), TLR4 DN, MyD88 DN, IRAK1 DN, TRAF6 DN, I B␣ DN, ERK2 DN, IKK␣ DN, WT IKK␣, IKK␤ DN, and WT IKK␤ have been previously described (31)(32)(33)(34)(35)(36)(37). The expression plasmid ERK1 DN was provided by Dr. Cobb (University of Texas Southwestern Medical Center, Dallas, TX).…”

Section: Plasmids Transfections and Luciferase Assaysmentioning

confidence: 99%

A Novel Role for IκB Kinase (IKK) α and IKKβ in ERK-Dependent Up-Regulation of MUC5AC Mucin Transcription by Streptococcus pneumoniae

Lim

Jono

et al. 2007

The Journal of Immunology

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Epithelial cells represent the first line of host innate defense against invading microbes by elaborating a range of molecules involved in pathogen clearance. In particular, epithelial mucins facilitate the mucociliary clearance by physically trapping inhaled microbes. Up-regulation of mucin production thus represents an important host innate defense response against invading microbes. How mucin is induced in upper respiratory Streptococcus pneumoniae infections is unknown. In this study, we show that pneumolysin is required for up-regulation of MUC5AC mucin via TLR4-dependent activation of ERK in human epithelial cells in vitro and in mice in vivo. Interestingly, a “second wave” of ERK activation appears to be important in mediating MUC5AC induction. Moreover, IκB kinase (IKK) α and IKKβ are distinctly involved in MUC5AC induction via an ERK1-dependent, but IκBα-p65- and p100-p52-independent, mechanism, thereby revealing novel roles for IKKs in mediating up-regulation of MUC5AC mucin by S. pneumoniae.

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“…Numerous in vivo and in vitro studies have examined the signaling events required for activation of respiratory epithelial cells by microbes (3,(8)(9)(10)(11). As in immune cells, the cellular response of epithelial cells activated by TLRs can be MyD88-dependent or -independent (12).…”

mentioning

confidence: 99%

FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells

Seiler

Hellberg

Lepper

et al. 2013

The Journal of Immunology

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Bacterial pathogens are a leading cause of lung infections and contribute to acute exacerbations in patients with chronic respiratory diseases. The innate immune system of the respiratory tract controls and prevents colonization of the lung with bacterial pathogens. Forkhead box transcription factor family O (FOXO) transcription factors are key regulators of cellular metabolism, proliferation, and stress resistance. In this study, our aim was to investigate the role of FOXO transcription factors in innate immune functions of respiratory epithelial cells. We show that bacterial pathogens potently activate FOXO transcription factors in cultured human respiratory epithelial cells in vitro. Infection of mice with bacterial pathogens resulted in the activation of FOXO transcription factors in alveolar and bronchial epithelial cells in vivo. Active FOXO was also detectable in human bronchial tissue obtained from subjects with different infection-related lung diseases. Small interfering RNA–mediated knockdown of FOXO in bronchial epithelial cells resulted in reduced expression of factors of the innate immune system such as antimicrobial peptides and proinflammatory cytokines, both under basal conditions and upon infection. FOXO deficiency further affected internalization of Haemophilus influenzae in bronchial epithelial cells. Finally, we show that TLR3 activates innate immune responses in a FOXO-dependent manner. In conclusion, FOXO transcription factors are involved in the cellular responses to bacterial stimuli and act as central regulators of innate immune functions in respiratory epithelial cells.

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Activation of NF-κB by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1-dependent NIK–IKKα/β–IκBα and MKK3/6–p38 MAP kinase signaling pathways in epithelial cells

Cited by 247 publications

References 40 publications

Ras effector pathways modulate scatter factor-stimulated NF-κB signaling and protection against DNA damage

Ras effector pathways modulate scatter factor-stimulated NF-κB signaling and protection against DNA damage

A Novel Role for IκB Kinase (IKK) α and IKKβ in ERK-Dependent Up-Regulation of MUC5AC Mucin Transcription by Streptococcus pneumoniae

FOXO Transcription Factors Regulate Innate Immune Mechanisms in Respiratory Epithelial Cells

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