Damage-Associated Molecular Patterns in Inflammatory Diseases

Roh, Jong Seong; Sohn, Dong Hyun

doi:10.4110/in.2018.18.e27

Cited by 813 publications

(633 citation statements)

References 92 publications

(125 reference statements)

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“…Therefore, the term host defense peptides (HDPs) was coined to encompass their pleiotropic nature, and association with both infectious as well as non-infectious inflammatory responses [12], although these two terms are used interchangeably. In the latter context, HDPs fit into the definition of "alarmins" or "danger signals", i.e., various endogenous molecules collectively known as DAMPs (damage associated molecular patterns), which are released from damaged or dying cells and initiate a diverse range of physiological and pathophysiological functions [13][14][15]. At present, HDPs are perceived as multifunctional agents that coordinate diverse immune surveillance functions necessary to maintain homeostasis ( Figure 1) [16].…”

Section: Introductionmentioning

confidence: 99%

Expression and Function of Host Defense Peptides at Inflammation Sites

Prasad

Fiedoruk

Daniluk

et al. 2019

IJMS

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There is a growing interest in the complex role of host defense peptides (HDPs) in the pathophysiology of several immune-mediated inflammatory diseases. The physicochemical properties and selective interaction of HDPs with various receptors define their immunomodulatory effects. However, it is quite challenging to understand their function because some HDPs play opposing pro-inflammatory and anti-inflammatory roles, depending on their expression level within the site of inflammation. While it is known that HDPs maintain constitutive host protection against invading microorganisms, the inducible nature of HDPs in various cells and tissues is an important aspect of the molecular events of inflammation. This review outlines the biological functions and emerging roles of HDPs in different inflammatory conditions. We further discuss the current data on the clinical relevance of impaired HDPs expression in inflammation and selected diseases.

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Section: Introductionmentioning

confidence: 99%

Expression and Function of Host Defense Peptides at Inflammation Sites

Prasad

Fiedoruk

Daniluk

et al. 2019

IJMS

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“…Accordingly, there is concentration of stress during dynamic functioning of large muscles. Given the modern understanding of how tissue injury and microdamage are capable of activating a wide array of pattern recognition receptors, then resident immunocytes at such points of high stress would run a high risk of activation . How is the potential for such locally concentrated firepower tamed to avoid what we would term “an immunological blitzkrieg” at the enthesis?…”

Section: The Enthesismentioning

confidence: 99%

“…Given the modern understanding of how tissue injury and microdamage are capable of activating a wide array of pattern recognition receptors, then resident immunocytes at such points of high stress would run a high risk of activation. 20,21 How is the potential for such locally concentrated firepower tamed to avoid what we would term "an immunological blitzkrieg" at the enthesis? The aforementioned fibrocartilage, analogous to articular cartilage, is completely avascular and in effect creates a "demilitarized immune buffer zone" at the sites of highest stress.…”

Section: What Is An Enthesis?mentioning

confidence: 99%

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Bridgewood

Sharif

Sherlock

et al. 2020

Immunological Reviews

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The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL‐23R or the interleukin‐23 (IL‐23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin‐17 (IL‐17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL‐23R–expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL‐23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL‐23R–expressing myeloid cells and various innate and adaptive T cells that produce IL‐17 family cytokines have also been described in the human enthesis. Blockade of IL‐23 pathway with either anti‐p40 or anti‐p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL‐23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue.

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“…Healthy neurons secrete factors such as TREM2 and fractalkine, and these signal by activating receptors present on microglia, maintaining the surveillance state of microglia. Following a brain insult, microglia are exposed to factors released due to cellular injury that may include nuclear or cytosolic proteins such as HMGB1, ATP, and heat shock proteins, or may include proteins released due to damaged extracellular matrix . In turn, microglia then attain an activated morphological state with retraction and hyperatrophied cellular processes, and release neuroinflammatory cytokines with the aim of clearing cellular debris after brain injury .…”

Section: Neuroinflammationmentioning

confidence: 99%

“…Following a brain insult, microglia are exposed to factors released due to cellular injury that may include nuclear or cytosolic proteins such as HMGB1, ATP, and heat shock proteins, or may include proteins released due to damaged extracellular matrix. 19 In turn, microglia then attain an activated morphological state with retraction and hyperatrophied cellular processes, and release neuroinflammatory cytokines with the aim of clearing cellular debris after brain injury. 20 The released cytokines and chemokines promote mobilization of additional immune cells to the site of injury, leading to their proliferation and activation.…”

Section: Key Pointsmentioning

confidence: 99%

Microglial polarization in posttraumatic epilepsy: Potential mechanism and treatment opportunity

et al. 2020

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Owing to the complexity of the pathophysiological mechanisms driving epileptogenesis following traumatic brain injury (TBI), effective preventive treatment approaches are not yet available for posttraumatic epilepsy (PTE). Neuroinflammation appears to play a critical role in the pathogenesis of the acquired epilepsies, including PTE, but despite a large preclinical literature demonstrating the ability of anti‐inflammatory treatments to suppress epileptogenesis and chronic seizures, no anti‐inflammatory treatment approaches have been clinically proven to date. TBI triggers robust inflammatory cascades, suggesting that they may be relevant for the pathogenesis of PTE. A major cell type involved in such cascades is the microglial cells—brain‐resident immune cells that become activated after brain injury. When activated, these cells can oscillate between different phenotypes, and such polarization states are associated with the release of various pro‐ and anti‐inflammatory mediators that may influence brain repair processes, and also differentially contribute to the development of PTE. As the molecular mechanisms and key signaling molecules associated with microglial polarization in brain are discovered, strategies are now emerging that can modulate this polarization, promoting this as a potential therapeutic strategy for PTE. In this review, we discuss the relevant literature regarding the polarization of brain‐resident immune cells following TBI and attempt to put into perspective a role in epilepsy pathogenesis. Finally, we explore potential strategies that could polarize microglia/macrophages toward a neuroprotective phenotype to mitigate PTE development.

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Damage-Associated Molecular Patterns in Inflammatory Diseases

Cited by 813 publications

References 92 publications

Expression and Function of Host Defense Peptides at Inflammation Sites

Expression and Function of Host Defense Peptides at Inflammation Sites

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

Microglial polarization in posttraumatic epilepsy: Potential mechanism and treatment opportunity

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