## 1 Introduction  
Periodontitis is a common chronic oral disease caused by mixed, predominantly Gram-negative, anaerobic, pathogenic microorganisms in close proximity to periodontal tissues [1]. Human hosts have various strategies for recognizing the molecular patterns of oral microbes, including those from the periodonontopathogens, which, in turn, trigger corresponding host immune reactions [2]. Periodontitis and its associated periodontium destruction is believed to be the result of damaging or inappropriate host responses induced by periodontalogens [3]. Lipopolysaccharide (LPS) is a cell wall component of Gram-negative bacteria, which are known to cause various reactions on the human host [4]. For instance, the recognition of LPS by myeloid and/or non-myeloid cells would activate the host's innate immune system to produce proinflammatory cytokines, including, but not limited to, tumor necrosis factors (TNF), interleukin (ILs), and cyclooxygenase-2 (COX-2) [5; 6]. Systemic exposure of LPS in high quantities causes the overproduction of cytokines, which induce fever, deteriorate organ perfusion, tempt cardiovascular collapse and eventually cause fatal sepsis syndrome [7]. Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are host cell receptors (surface or intracellular) responsible for various innate immune responses in mammals [8; 9]. TLRs and NLRs represent two large families of proteins in charge of responses mediation via nuclear factor-xB (NF-xB)-dependent/interferon-regulatory factor-dependent signaling pathways, or NF-xB-dependent/mitogen-activated protein kinase signaling pathways [8; 9]. It is speculated that the recognition of LPS is mediated by these two pattern-recognition receptors when Gram-negative pathogenic microorganisms get into close contact with host cells. Previous reports indicated that TLR2/4 are essential LPS-recognition receptors at the human periodontium [10], while in general, TLR2 appeared to be less specific than TLR4 in sensing LPS [11], the reason being that the former covers more ligands, whereas TLR4 targets LPS, specifically. TLR2 needs to form heterodimers, such as TLR1/2 or TLR2/6, to function and such heterodimers have to be formed before periodontitis and/or LPS can be recognized [12]. It is speculated that, nevertheless, TLR1/2 andTLR2/6 expand the receptor-ligand recognition spectrum and improve the immune reactions to Gram-negative bacteria [12]. Previous research has demonstrated the expression of TLR1-10 in 10 chronic periodontitis and healthy samples; however, the expression of those receptors in junctional epithelium was not reported [13]. Given that anaerobic, Gram-negative pathogens are key agents for periodontitis pathogenesis, the nature of the hypoxic micro-environment draws attentions of researchers interested in deciphering the complicated pathogenic process [14]. At sea level, atmospheric oxygen level at 760 mm Hg is 21% or 140-150 mm Hg, while the corresponding alveolar O\({}_{2}\) partial pressure (PO\({}_{2}\)) is approximately 100 mm Hg in healthy human [15]. In chronic, inflamed periodontitis tissue, oxygen level could be at \(<\)50% O\({}_{2}\) saturation or as low as 7 mm Hg [16; 17], compared to 85% O\({}_{2}\) saturation or up to 52 mm Hg at less affected gingivitis compartments [16]. Inside periodontal pockets, O\({}_{2}\) is persistently consumed and reduced to low levels due to increased consumption via active chronic inflammatory cellular processes as well as the diminished oxygen availability through thrombosis of the involved micro- vasculature [14; 18]. Therefore, hypoxia establishes and potentially sustains the survival of facultative and obligatory anaerobes, promotes periodontal inflammation and, in turn, could intensify and worsen periodontitis development. On the contrary, a hypoxic environment, however, was known to relate to cell survival, DNA repair, apoptosis, etc., driven by an array of corresponding signals transcription in [19].