PMC

(A) Maxillary molar arcade of a mouse with normal dentition and tight gingival sulci (arrowhead). (B) Maxillary molar arcade demonstrating extreme expansion of the lingual and buccal gingival sulci with hair. Note the separation and rotation of M1 and M2 and the distance between M2 and M3 in the arcade (*).

Spontaneous bleeding from gingival sulci after a bite by a West African saw-scaled viper (Echis ocellatus) in Nigeria

(a) Osteoclastogenic effect of rGGT administration. rGGT was administered to the anterior maxillary gingival sulci of WT mice and Tlr4^−/− mice. AB, alveolar bone; T, tooth; G, gingiva. Scale: 500 μm. The number of osteclasts was assessed by counting TRAP-positive cells within the sections. Data are expressed as the mean ± SD (n = 3). *p < 0.05; **p < 0.01. (b) Proinflammatory effect of rGGT administration. rGGT was administered to the labial gingival sulci in the upper incisor of WT mice and Tlr4^−/− mice. The sections of the gingiva were stained with H&E. The magnified image of the administration site is shown in the right panel. Scale: 100 μm. The number of inflammatory cells was assessed by microscopic counting of hematoxylin-positive polymorphonuclear cells (neutrophils) within the sections. Data are expressed as the mean ± SD (n = 4). *p < 0.05.

Pathways represent the proposed activity in the periodontium and in the liver in GFPWT:WT (A) and GFP-WT:KO chimeras (B) following LPS application to the gingival sulcus. (A) LPS from gram negative bacteria is released in the gingival sulci where it acts as a chemoattractant. Macrophages (TLR4+/+) from circulating blood migrate to the gingival tissues where they are activated by LPS and secrete proinflammatory cytokines such as TNFα, IL1β and IL6. These cytokines and/or LPS enter the circulation and eventually reach the liver. Liver Kupffer cells that reside in sinusoids will be exposed to either LPS and/or proinflammatory cytokines. In GFPWT:WT animals Kupffer cells are TLR4+/+ and will respond to LPS by synthesizing and secreting proinflammatory cytokines resulting in impaired ipGTT. In addition, cytokines from the circulation can impair insulin signaling pathway in hepatocytes. (B) In GFPWT:KO animals, Kupffer cells are TLR4-/- and if the major stimulus to the liver Kupffer cells is LPS, ipGTT in these animals will be normal. However, circulating proinflammatory cytokines may act directly on hepatocytes leading to impaired ipGTT. IR: insulin resistance, ipGTT: intraperitoneal glucose tolerance test.