Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons

Santoni, Giorgio; Cardinali, Claudio; Morelli, Maria Beatrice; Santoni, Matteo; Nabissi, Massimo; Amantini, Consuelo

doi:10.1186/s12974-015-0239-2

Cited by 139 publications

(104 citation statements)

References 129 publications

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“…Decades ago, Janeway proposed a hypothesis that innate immune cells utilize germline-encoded receptors that are antigen-selective [68], and such receptors were eventually identified many years later. Innate immune cells express pattern-recognition receptors that bind conserved molecular patterns, and engagement of these receptors transduces a signal allowing cells to sense danger in the form of a pathogen or host cellular damage [69, 70]. These receptors are present at the cell surface, in endocytic organelles, or in the cytoplasm permitting perception of both extracellular and intracellular dangers.…”

Section: Toll-like Receptor Familymentioning

confidence: 99%

“…The apparent paradox of sterile inflammation is resolved by realization that pattern-recognition receptors, including TLRs, recognize endogenous ligands. The endogenous molecules called damage-associated molecular patterns (DAMPs) are created or released upon tissue injury or cell death [69, 76]. Heat shock protein 60 was the first candidate DAMP reported to induce TLR4 activation [83].…”

Section: Toll-like Receptor Familymentioning

confidence: 99%

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Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

McCoy

2016

Mediators of Inflammation

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Since the discovery of the endocannabinoid system consisting of cannabinoid receptors, endogenous ligands, and biosynthetic and metabolizing enzymes, interest has been renewed in investigating the promise of cannabinoids as therapeutic agents. Abundant evidence indicates that cannabinoids modulate immune responses. An inflammatory response is triggered when innate immune cells receive a danger signal provided by pathogen- or damage-associated molecular patterns engaging pattern-recognition receptors. Toll-like receptor family members are prominent pattern-recognition receptors expressed on innate immune cells. Cannabinoids suppress Toll-like receptor-mediated inflammatory responses. However, the relationship between the endocannabinoid system and innate immune system may not be one-sided. Innate immune cells express cannabinoid receptors and produce endogenous cannabinoids. Hence, innate immune cells may play a role in regulating endocannabinoid homeostasis, and, in turn, the endocannabinoid system modulates local inflammatory responses. Studies designed to probe the interaction between the innate immune system and the endocannabinoid system may identify new potential molecular targets in developing therapeutic strategies for chronic inflammatory diseases. This review discusses the endocannabinoid system and Toll-like receptor family and evaluates the interaction between them.

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Section: Toll-like Receptor Familymentioning

confidence: 99%

Section: Toll-like Receptor Familymentioning

confidence: 99%

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

McCoy

2016

Mediators of Inflammation

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“…This signal is processed centrally and causes a reflex decrease in sympathetic input to the heart and vasculature as well as an increase in vagal parasympathetic input to the heart. Analogous processes occur during reflex activation of the immune system, but the stimuli that activate afferent nerves during reflex modulation of the immune system are chemicals generated at sites of inflammation or injury (Bonaz et al, 2016b; Santoni et al, 2015). These include pathogen associated molecular patterns, danger associated molecular patterns, and cytokines/chemokines released in response to the former.…”

Section: Introductionmentioning

confidence: 99%

Cholinergic modulation of the immune system presents new approaches for treating inflammation

Hoover

2017

Pharmacology & Therapeutics

240

169

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The nervous system and immune system have broad and overlapping distributions in the body, and interactions of these ubiquitous systems are central to the field of neuroimmunology. Over the past two decades, there has been explosive growth in our understanding of neuroanatomical, cellular, and molecular mechanisms that mediate central modulation of immune functions through the autonomic nervous system. A major catalyst for growth in this field was the discovery that vagal nerve stimulation (VNS) caused a prominent attenuation of the systemic inflammatory response evoked by endotoxin in experimental animals. This effect was mediated by acetylcholine (ACh) stimulation of nicotinic receptors on splenic macrophages. Hence, the circuit was dubbed the “cholinergic anti-inflammatory pathway”. Subsequent work identified the α7 nicotinic ACh receptor (α7nAChR) as the crucial target for attenuation of pro-inflammatory cytokine release from macrophages and dendritic cells. Further investigation made the important discovery that cholinergic T cells within the spleen and not cholinergic nerve cells were the source of ACh that stimulated α7 receptors on splenic macrophages. Given the important role that inflammation plays in numerous disease processes, cholinergic anti-inflammatory mechanisms are under intensive investigation from a basic science perspective and in translational studies of animal models of diseases such as inflammatory bowel disease and rheumatoid arthritis. This basic work has already fostered several clinical trials examining the efficacy of VNS and cholinergic therapeutics in human inflammatory diseases. This review provides an overview of basic and translational aspects of the cholinergic anti-inflammatory response and relevant pharmacology of drugs acting at the α7nAChR.

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“…Different types of inflammasomes generate innate immune responses in different brain cells. Accumulating evidence suggests that the NLRP3 inflammasome is activated in microglia (de Rivero Vaccari et al, 2014; Santoni et al, 2015). Microglia cells are the resident macrophage in the brain and play an important role in modulating inflammatory response induced by ICH (Lan et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

Yang

Sun

Kim

et al. 2018

Experimental Neurology

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Nucleotide-binding and oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, which is composed of an NLRP3 domain, the adaptor molecule apoptosis-associated speck-like protein containing a CARD (ASC) domain, and procaspase-1, plays an important role in the immune pathophysiology of the secondary damage induced by intracerebral hemorrhage (ICH). This study aims to investigate whether pre-stroke treatment with fimasartan, an angiotensin II receptor blocker, has anti-inflammatory effects on ICH by inhibiting the activation of the NLRP3 inflammasome. Sprague-Dawley rats were divided into five groups: sham, vehicle, low-dose (0.5 mg/kg) and regular-doses (1.0 and 3.0 mg/kg) fimasartan. These rats were treated for 30 days before the induction of collagenase-induced ICH and continuously 3 days after surgery. The mean blood pressure (BP) in the low-dose fimasartan group was not significantly different from that of control, and BP in the regular-dose groups was decreased in a dose-dependent manner. Pretreatment with low-dose fimasartan attenuated ICH-induced edema and improved neurological functions. Activation of the NLRP3/ASC/caspase-1 and the NF-κB pathways after ICH was markedly reduced by low-dose fimasartan. The double immunofluorescence staining of brain cells showed a significant decrease in the co-localization of NLRP3 with Iba1 (microglia marker) positive cells by fimasartan treatment. Cultured microglia cells stimulated by hemolysate demonstrated significant activation of the inflammasome, which was reduced by fimasartan. Pretreatment with a low-dose fimasartan alleviated brain damage after acute ICH by inhibiting the NLRP3 inflammasome without lowering MBP. Our study suggests pre-stroke administration of fimasartan could potentially attenuate ICH-induced secondary brain injury by targeting the inflammasome.

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Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons

Cited by 139 publications

References 129 publications

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

Interaction between Cannabinoid System and Toll-Like Receptors Controls Inflammation

Cholinergic modulation of the immune system presents new approaches for treating inflammation

Pretreatment with low-dose fimasartan ameliorates NLRP3 inflammasome-mediated neuroinflammation and brain injury after intracerebral hemorrhage

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