The NF-κB (nuclear factor κ-light-chain-enhancer of activated B cells) transcription factor family is a pleiotropic regulator of many cellular signaling pathways, providing a mechanism for the cells in response to a wide variety of stimuli linking to inflammation. The stimulated cells will be regulated by not only the canonical but also non-canonical NF-κB pathways. To initiate both of these pathways, IκB-degradation triggers NF-κB release and the nuclear translocated-heterodimer (or homodimer) can associate with the κB sites of promoter to regulate the gene transcriptions. NF-κB ubiquitously expresses in neurons and the constitutive NF-κB activation is associated with processing of neuronal information. NF-κB can regulate the transcription of genes such as chemokines, cytokines, proinflammatory enzymes, adhesion molecules, proinflammatory transcription factors, and other factors to modulate the neuronal survival. In neuronal insult, NF-κB constitutively active in neuron cell bodies can protect neurons against different injuries and regulate the neuronal inflammatory reactions. Besides neurons, NF-κB transcription factors are abundant in glial cells and cerebral blood vessels and the diverse functions of NF-κB also regulate the inflammatory reaction around the neuronal environment. NF-κB transcription factors are abundant in the brain and exhibit diverse functions. Several central nerve system (CNS) diseases are linked to NF-κB activated by inflammatory mediators. The RelA and c-Rel expression produce opposite effects on neuronal survival. Importantly, c-Rel expression in CNS plays a critical role in anti-apoptosis and reduces the age-related behaviors. Moreover, the different subunits of NF-κB dimer formation can modulate the neuroninflammation, neuronal protection, or neurotoxicity. The diverse functions of NF-κB depend on the subunits of the NF-κB dimer-formation which enable us to develop a therapeutic approach to neuroinflammation based on a new concept of inflammation as a strategic tool in neuronal cells. However, the detail role of NF-κB in neuroinflammation, remains to be clarified. In the present article, we provide an updated review of the current state of our knowledge about relationship between NF-κB and neuroinflammation.

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Reactive oxygen species (ROS), a redox signal, are produced by various enzymatic reactions and chemical processes, which are essential for many physiological functions and act as second messengers. However, accumulating evidence has implicated the pathogenesis of several human diseases including neurodegenerative disorders related to increased oxidative stress. Under pathological conditions, increasing ROS production can regulate the expression of diverse inflammatory mediators during brain injury. Elevated levels of several proinflammatory factors including cytokines, peptides, pathogenic structures, and peroxidants in the central nervous system (CNS) have been detected in patients with neurodegenerative diseases such as Alzheimer's disease (AD). These proinflammatory factors act as potent stimuli in brain inflammation through upregulation of diverse inflammatory genes, including matrix metalloproteinases (MMPs), cytosolic phospholipase A2 (cPLA2), cyclooxygenase-2 (COX-2), and adhesion molecules. To date, the intracellular signaling mechanisms underlying the expression of target proteins regulated by these factors are elusive. In this review, we discuss the mechanisms underlying the intracellular signaling pathways, especially ROS, involved in the expression of several inflammatory proteins induced by proinflammatory factors in brain resident cells. Understanding redox signaling transduction mechanisms involved in the expression of target proteins and genes may provide useful therapeutic strategies for brain injury, inflammation, and neurodegenerative diseases.

In respiratory diseases, there is an increased expression of multiple inflammatory proteins in the respiratory tract, including cytokines, chemokines, and adhesion molecules. Chemokines have been shown to regulate inflammation and immune cell differentiation. Moreover, many of the known inflammatory target proteins, such as matrix metalloproteinase-9 (MMP-9), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), cyclooxygenase-2 (COX-2), and cytosolic phospholipase A2 (cPLA2), are associated with airway and lung inflammation in response to various stimuli. Injuriously environmental stimuli can access the lung through either the airways or the pulmonary and systemic circulations. The time course and intensity of responses by resident and circulating cells may be regulated by various inflammatory signalings, including Src family kinases (SFKs), protein kinase C (PKC), growth factor tyrosine kinase receptors, nicotinamide adenine dinucleotide phosphate (NADPH)/reactive oxygen species (ROS), PI3K/Akt, MAPKs, nuclear factor-kappa B (NF-κB), activator protein-1 (AP-1), and other signaling molecules. These signaling molecules regulate both key inflammatory signaling transduction pathways and target proteins involved in airway and lung inflammation. Here, we discuss the mechanisms involved in the expression of inflammatory target proteins associated with the respiratory diseases. Knowledge of the mechanisms of inflammation regulation could lead to the pharmacological manipulation of anti-inflammatory drugs in the respiratory diseases.

Heme oxygenase‐1 (HO‐1) is a stress‐inducible rate‐limiting enzyme in heme degradation, which confers cytoprotection against oxidative injury and provides a vital function in maintaining tissue homeostasis. Increasing reports have indicated that lipoteichoic acid (LTA) exerts as LPS as an immune system‐stimulating agent and plays a role in the pathogenesis of severe inflammatory responses induced by Gram‐positive bacteria infection. Here, we report that LTA is an inducer of HO‐1 and examine the signaling pathways by which LTA regulates HO‐1 expression in human tracheal smooth muscle cells (HTSMCs). LTA induced HO‐1 protein, mRNA expression, and HO‐1 promoter activity. LTA‐stimulated HO‐1 expression was attenuated by transfection with dominant negative mutants of Toll‐like receptor‐2 (TLR‐2) and MyD88, the NADPH oxidase inhibitor (DPI), the ROS scavenger (NAC), and transfection with siRNAs of Src and NF‐E2‐related factor 2 (Nrf2). LTA‐stimulated c‐Src phosphorylation, translocation of p47phox and Nrf2, and ROS production were attenuated by transfection with dominant negative mutants of TLR‐2, MyD88, and c‐Src, and by pretreatment with DPI or NAC. Further studies revealed that LTA induced TLR‐2, MyD88, c‐Src, and p47phox complex formation. These results demonstrated that in HTSMCs, LTA induced ROS generation through the TLR‐2/MyD88/c‐Src/NADPH oxidase pathway, in turn initiates the activation of Nrf2, and ultimately induces HO‐1 expression.