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Mediators of Periodontal Tissues, Lymphocytes, T helper = CD4+ cells.…

- - - - Neutrophil Elastase
        
        Disruption of Gingival Epithelial Barrier: NE cleaves cell adhesion molecules such as desmoglein 1, occludin, and E-cadherin, leading to the disruption of the gingival epithelial barrier. This disruption facilitates bacterial invasion and exacerbates inflammation in periodontal tissues
        
        Upregulation of Proinflammatory Cytokines: NE can upregulate the expression of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. This cytokine release further amplifies the inflammatory response, contributing to tissue destruction and bone loss... Degradation of Periodontal Ligament: NE degrades noncollagenous proteins that provide mechanical strength to the periodontal ligament, leading to its initial destruction in the early stages of periodontal disease...
        
        .. Induction of Neutrophil Extracellular Traps (NETs): NE is involved in the formation of NETs, which are associated with the pathogenesis of chronic inflammatory diseases, including periodontitis. Elevated levels of NE and NET components in saliva correlate with clinical attachment loss in periodontitis patients.Degrades Type IV and V collagen active in disease and remodeling process
        
        Neutrophil elastase (NE) is a serine protease found in neutrophils, which plays a crucial role in the immune response by degrading pathogens and modulating inflammation. Neutrophil extracellular traps (NETs) are web-like structures composed of decondensed chromatin DNA, histones, and various antimicrobial proteins, including NE and myeloperoxidase (MPO). NETs serve to trap and kill pathogens,
      - MMP-8 Neutrophil Collagenase)
        
        Matrix metalloproteinase-8 (MMP-8) plays a significant role in the pathogenesis of periodontal disease. MMP-9, a member of the MMP family, is a zinc-dependent endopeptidase that degrades components of the extracellular matrix (ECM), particularly type IV and V collagens, which are crucial for maintaining the structural integrity of periodontal tissues.
        
        MMP-8, or matrix metalloproteinase-8, is a type of collagenase, specifically gelatinase B, and is primarily produced by neutrophils. It's involved in tissue remodeling, wound healing, and inflammation, and its activity is linked to the extent of cellular inflammation. MMP-8 is also involved in the mobilization of tissue-bound growth factors and cytokines, and its release from neutrophils can contribute to the degradation of the extracellular matrix (ECM)
      - Cathepsin G
        
        It is a serine protease predominantly found in polymorphonuclear neutrophilic leukocytes (PMNs) and monocyte/macrophage-like cells. cathepsin G is involved in both direct and indirect mechanisms of tissue destruction. Directly, it contributes to the degradation of periodontal tissues. Indirectly, it activates latent neutrophil procollagenase (proMMP-8),
        
        cathepsin G has been shown to mediate inflammatory responses. For instance, it activates caspase-4 in human gingival fibroblasts in response to bacterial surface proteins, leading to pyroptosis and the secretion of pro-inflammatory cytokines such as IL-1α
- - - - Gq: Phospholipase C activation
      - Gi: Ras/ERK pathway activation
      - Gβγ: Triggers downstream pathways
      - 3. Secondary Messenger Activation
        
        PLCβ cleaves PIP2 → forms IP3 and DAG
        
        IP3 → Releases intracellular Ca²⁺
        
        DAG → Activates PKC isoforms
        
        Increased cytosolic Ca²⁺ and actin polymerization
        
        4. Polarization and Chemotaxis
        
        Actin cytoskeleton reorganization via Rho/Rac/Cdc42
        
        Formation of lamellipodia and uropods (RUFFLING)
        
        Directed migration along chemotactic gradients
        
        5. Adhesion and Rolling
        
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